Publications by authors named "Hye Seung Han"

95 Publications

Fatty acid synthetase expression in triple-negative breast cancer.

J Pathol Transl Med 2022 Mar 21;56(2):73-80. Epub 2022 Jan 21.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Background: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism-related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.

Methods: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0-1+ FASN staining were grouped as low-grade FASN and patients with 2-3+ FASN staining as high-grade FASN.

Results: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.

Conclusions: We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.
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http://dx.doi.org/10.4132/jptm.2021.10.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935000PMC
March 2022

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms.

J Pathol Transl Med 2021 Jul 8;55(4):247-264. Epub 2021 Jul 8.

Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the "Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm" to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.
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http://dx.doi.org/10.4132/jptm.2021.05.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353140PMC
July 2021

High Concordance of Genomic Profiles between Primary and Metastatic Colorectal Cancer.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Department of Pathology, School of Medicine, Konkuk University, Seoul 05030, Korea.

The comparison of the genetic profiles between primary and metastatic colorectal cancer (CRC) is needed to enable the discovery of useful therapeutic targets against metastatic CRCs. We performed the targeted next generation sequencing assay of 170 cancer-associated genes for 142 metastatic CRCs, including 95 pairs of primary and metastatic CRCs, to reveal their genomic characteristics and to assess the genetic heterogeneity. The most frequently mutated gene in primary and metastatic CRCs was (71% vs. 65%), (54% vs. 57%), (45% vs. 44%), (16% vs. 19%), (15% vs. 14%) and (11% vs. 11%). The concordance in the top six frequently mutated genes was 85%, on average. The overall mutation frequencies were consistent with two sets of public data (TCGA and MSKCC). To the author's knowledge, this is the first study to compare the genetic profiles of our cohort with that of the metastatic CRCs from MSKCC. Comparative sequencing analysis between primary and metastatic CRCs revealed a high degree of genetic concordance in the current clinically actionable genes. Therefore, the genetic investigation of archived primary tumor samples with the challenges of obtaining an adequate sample from metastatic sites appears to be sufficient for the application of cancer precision medicine in the metastatic setting.
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http://dx.doi.org/10.3390/ijms22115561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197329PMC
May 2021

Concordance of Programmed Death-Ligand 1 Expression between SP142 and 22C3/SP263 Assays in Triple-Negative Breast Cancer.

J Breast Cancer 2020 Jun 1;23(3):303-313. Epub 2020 Jun 1.

Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.

Purpose: Triple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs).

Methods: Immunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs.

Results: At the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased. The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower.

Conclusion: This study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.
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http://dx.doi.org/10.4048/jbc.2020.23.e37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311361PMC
June 2020

Histology and its prognostic effect on -mutated colorectal carcinomas in Korea.

Oncol Lett 2020 Jul 13;20(1):655-666. Epub 2020 May 13.

Department of Pathology, Konkuk University School of Medicine, Seoul 05030, Republic of Korea.

mutation is frequently identified in advanced colorectal carcinoma (CRC); however, its prognostic significance and the associated histological features have remained to be clarified. In the present study, the precise histological results and prognostic value of -mutated CRCs were investigated in patients from South Korea. A retrospective review of the results from mutation testing, as well as evaluation of the histology of 310 cases of CRC at various stages, were performed. Cross-tabulation and survival analysis were performed according to the status. Patients with mutation more frequently exhibited serrated and papillary architectures (P=0.009 and P=0.014, respectively). mutation was an independent unfavorable prognostic factor for overall survival (OS) according to multivariate analysis (P=0.001), whereas no association was observed with disease-free survival (DFS) (P=0.611). Of note, in the subgroup of -mutated carcinomas, the presence of a solid component on histology was associated with less favorable OS (P=0.032). Furthermore, among the wild type cases, patients with a micropapillary component had a worse OS than those who did not (P=0.018). However, no subgroup or specific histological features were associated with DFS. In summary, -mutated CRCs had a moderate association with particular histological features, and according to the mutational status, there was a certain degree of association between histology and prognosis.
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http://dx.doi.org/10.3892/ol.2020.11606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285809PMC
July 2020

Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid-enhanced MRI: A Multicenter Study.

Radiology 2020 08 2;296(2):335-345. Epub 2020 Jun 2.

From the Department of Radiology, Seoul National University Hospital, Seoul, Korea (I.J., J.M.L.); Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea (S.Y.K.); Department of Radiology, Samsung Medical Center, Seoul, Korea (T.W.K., Y.K.K.); Department of Radiology, Korea University Anam Hospital, Seoul, Korea (B.J.P.); Department of Radiology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (Y.J.L.); Department of Radiology, Seoul St. Mary's Hospital, Seoul, Korea (J.I.C.); Department of Radiology, Korea University Guro Hospital, Seoul, Korea (C.H.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Korea (H.S.P.); Department of Pathology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea (K.L., H.K.); Department of Pathology, Asan Medical Center, Seoul, Korea (E.Y., H.J.K.); Department of Pathology, Samsung Medical Center, Seoul, Korea (S.Y.H.); Department of Pathology, Korea University Anam Hospital, Seoul, Korea (J.Y.K.); Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (S.A.); Department of Pathology, Seoul St. Mary's Hospital, Seoul, Korea (E.S.J.); Department of Pathology, Korea University Guro Hospital, Seoul, Korea (B.H.K.); and Department of Pathology, Konkuk University Hospital, Seoul, Korea (H.S.H.).

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; = .01) and MRI features including well-defined margin (odds ratio, 5.5; = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; < .001), and restricted diffusion (odds ratio, 1.9; = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 See also the editorial by Motosugi in this issue.
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http://dx.doi.org/10.1148/radiol.2020192275DOI Listing
August 2020

Case report of periorbital metastasis from rectal cancer.

Medicine (Baltimore) 2020 Jan;99(1):e18479

Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Gwangjin-gu, Seoul, Republic of Korea.

Introduction: Periorbital metastasis of colorectal cancer is rare. Therefore, herein, we report a patient with rectal cancer who presented with periorbital metastasis without any systemic metastasis.

Patient Concerns: The patient was a 57-year-old man who had a painless nodule on his left eyelid.

Diagnosis: The patient presented with loose and frequent stools and was diagnosed with rectal adenocarcinoma via colonoscopic biopsy at the local clinic. Curative resection (low anterior resection with temporary ileostomy formation) was performed 4 weeks after completing chemoradiotherapy. The final TNM stage was yp stage T2N0M0. Eight months after the diagnosis of rectal cancer, a protruding lesion was noticed on the patient's left eyelid. Histologic evaluation of the nodule revealed metastatic adenocarcinoma of rectal cancer.

Interventions: The patient received neoadjuvant chemoradiotherapy and curative resection for rectal cancer. After excision of the periorbital nodule, he received 5 cycles of chemotherapy.

Outcomes: The patient underwent regular follow-up because he was not able to endure chemotherapy; no recurrence has been observed 21 months after the diagnosis of rectal cancer. Histologic examination revealed metastatic adenocarcinoma of rectal cancer on the patient's left eyelid. However, consecutive imaging studies revealed no other metastatic lesions. Finally, the patient was diagnosed with a solitary periorbital metastasis of rectal cancer.

Conclusion: This case report helps in understanding the course of progression from rectal cancer to periorbital metastasis.
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http://dx.doi.org/10.1097/MD.0000000000018479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946509PMC
January 2020

Standardized Pathology Report for Colorectal Cancer, 2nd Edition.

J Pathol Transl Med 2020 Jan 13;54(1):1-19. Epub 2019 Nov 13.

Department of Pathology, Kyung Hee University College of Medicine, Seoul, Korea.

The first edition of the 'Standardized Pathology Report for Colorectal Cancer,' which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of "standard data elements" and "conditional data elements." Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as "standard data elements," while other prognostic factors and factors related to adjuvant therapy are classified as "conditional data elements" so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.
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http://dx.doi.org/10.4132/jptm.2019.09.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986966PMC
January 2020

Cross-national analysis about the difference of histopathological management in Tis and T1 colorectal cancer between Japan and Korea.

J Anus Rectum Colon 2019 29;3(1):18-26. Epub 2019 Jan 29.

Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.

Objectives: There are differences in each country with regards to histopathological managements of colorectal cancer (CRC), such as definition of Tis and lymphatic and venous invasion. In this study, we compared Tis and T1 CRC in Japan and Korea.

Methods: We retrospectively compared various clinical characteristics of consecutive patients who had Tis and T1 CRCs and who were newly diagnosed between 2010 and 2014 at the Kyoto Prefectural University of Medicine (Japan) and the Konkuk University (Korea).

Results: Three hundred and sixty-five cases of T1 cancer and 510 cases of Tis cancer from 726 Japanese and 149 Korean patients were included. The rate of Tis in Japan was higher than in Korea (59.8% vs. 51.0%, = 0.047), according to the difference of definition of Tis. In the analyses of 365 T1 CRCs, median age was higher in Japan than Korea (67.8 ± 10.6 vs. 62.2 ± 10.1, < 0.001). Right-sided lesions were more frequent in Japan than they were in Korea (38.7% vs. 22.2%, < 0.001). The rates of venous and lymphatic invasion were higher in Japan than they were in Korea (venous: 18.6% vs. 1.4%, < 0.001, lymphatic: 25.3% vs. 13.7%, = 0.042), according to the different methods of immunohistochemical examinations used (Japan: E-HE and D2-40, Korea: ERG).

Conclusions: Our study of T1 CRC showed that there were differences between Japan and Korea in tumor location, elderly incidence, and histopathological lymphatic and venous invasion. Additionally, rates of Tis were different between the two countries. In this international study for CRC, it is considered that we have to pay attention regarding the difference of histopathological definition and method in each country.
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http://dx.doi.org/10.23922/jarc.2017-031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752126PMC
January 2019

Assessing significant fibrosis using imaging-based elastography in chronic hepatitis B patients: Pilot study.

World J Gastroenterol 2019 Jul;25(25):3256-3267

Department of Internal Medicine, Konkuk University School of Medicine, Seoul 05030, South Korea.

Background: Accurate detection of significant fibrosis (fibrosis stage 2 or higher on the METAVIR scale) is important especially for chronic hepatitis B (CHB) patients with high viral loads but with normal or mildly elevated alanine aminotransferase (ALT) levels because the presence of significant fibrosis is accepted as the indication for antiviral treatment. Liver biopsy is the reference standard for diagnosing significant fibrosis, but it is an invasive procedure. Consequently, noninvasive imaging-based measurements, such as magnetic resonance elastography (MRE) or two-dimensional shear-wave elastography (2D-SWE), have been proposed for the quantitative assessment of liver fibrosis.

Aim: To explore MRE and 2D-SWE to identify fibrosis stage, and to compare their performance with that of serum-based indices.

Methods: The study enrolled 63 treatment-naïve CHB patients with high viral loads but with normal or mildly elevated ALT levels who underwent liver biopsy before a decision was made to initiate antiviral therapy. MRE and 2D-SWE were performed, and serum-based indices, such as FIB-4 and aspartate transaminase to platelet ratio index (APRI), were calculated. The diagnostic performances of MRE, 2D-SWE, FIB-4, and APRI for assessing significant fibrosis (≥ F2) and cirrhosis (F4) were evaluated with liver histology as the reference standard, using receiver operating characteristic analyses.

Results: The liver fibrosis stage was F0/F1 in 19, F2 in 14, F3 in 14, and F4 in 16 patients, respectively. MRE significantly discriminated F2 from F0/1 ( = 0.022), whereas 2D-SWE showed a broad overlap in distinguishing those stages. MRE showed a higher correlation coefficient value with fibrosis stage than 2D-SWE with fibrosis stage (0.869 0.649, Spearman test; < 0.001). Multivariate linear regression analyses showed that fibrosis stage was the only factor affecting the values of MRE ( < 0.001), whereas body mass index ( = 0.042) and fibrosis stage ( < 0.001) were independent factors affecting 2D-SWE values. MRE performance for diagnosing significant fibrosis was better [area under the curve (AUC) = 0.906, positive predictive value (PPV) 97.3%, negative predictive value (NPV) 69.2%] than that of FIB-4 (AUC = 0.697, = 0.002) and APRI (AUC = 0.717, = 0.010), whereas the performance of 2D-SWE (AUC = 0.843, PPV 86%, NPV 65%) was not significantly different from that of FIB-4 or APRI.

Conclusion: Compared to SWE, MRE might be more precise non-invasive assessment for depicting significant fibrosis and for making-decision to initiate antiviral-therapy in treatment-naïve CHB patients with normal or mildly-elevated ALT levels.
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http://dx.doi.org/10.3748/wjg.v25.i25.3256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626721PMC
July 2019

Comprehensive analysis for diagnosis of preoperative non-invasive follicular thyroid neoplasm with papillary-like nuclear features.

PLoS One 2019 5;14(7):e0218046. Epub 2019 Jul 5.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.

Objective: The current paradigm in the treatment of patients with non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a diagnostic lobectomy rather than complete thyroidectomy and postoperative radioiodine treatment. Consequently, preoperative diagnosis of NIFTP is considered to be important.

Methods: We performed the comprehensive analysis for diagnosis of preoperative 20 NIFTPs in comparison with 41 invasive encapsulated follicular papillary thyroid carcinomas (I-EFVPTCs) using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and molecular analysis for BRAF and RAS mutations.

Results: K-TIRADS 3 was identified as the most common sonographic diagnosis in both NIFTP and I-EFVPTC. Unlike I-EFVPTC, K-TIRADS 5 was not identified in NIFTP. AUS/FLUS was the most common cytopathological diagnosis and none of the cases were classified as malignant category in both groups, although the difference in distribution was not significant between the groups. BRAF mutation was not found in NIFTP but was present in 9.8% of cases in I-EFVPTC. The frequency of RAS mutation in I-EFVPTCs was twice as high as that of NIFTP. Wild-type BRAF and RAS in NIFTP was significantly higher than I-EFVPTC.

Conclusion: The existence of overlapping features between the groups was evident, hence conclusive distinction between radiology, cytology and molecular analysis could not be achieved. Apparently, the diagnosis of NIFTP based on comprehensive analysis was not confirmable but could perceive or at least favor the diagnosis of NIFTP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218046PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611592PMC
February 2020

Correlations of the Gastric and Duodenal Microbiota with Histological, Endoscopic, and Symptomatic Gastritis.

J Clin Med 2019 Mar 5;8(3). Epub 2019 Mar 5.

R&D Center, BioCore. Co. Ltd., Seoul 08511, Korea.

Mucosal inflammation is characterized by neutrophil and mononuclear cell infiltration. This study aimed to determine the gastric and duodenal microbiota associated with histological, endoscopic, and symptomatic gastritis. Dyspeptic adults who presented for evaluation were included. Subjects with either comorbidities or recent drug intake were excluded. Three endoscopic biopsies were obtained from the antrum, body, and duodenum. Next-generation sequencing for 16S ribosomal RNA V1⁻V2 hypervariable regions was performed. The correlation between the composition of microbiota and the degree of inflammatory cell infiltration, endoscopic findings, and Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) score was analyzed. In 98 included subjects, microbial communities in the antrum and body showed Bray⁻Curtis similarity; however, those in the duodenum showed dissimilarity. Histological and endoscopic gastritis was associated with the abundance of and that of commensal bacteria in the stomach. The abundances of and were correlated with histological gastritis, but not with endoscopic or symptomatic gastritis. The total PAGI-SYM score showed a stronger correlation with the duodenal microbiota ( and ) than with the gastric microbiota (, , and ). Different correlations of the gastric and duodenal microbiota with histological, endoscopic, and symptomatic gastritis were observed for the first time at the species level. -negative gastritis is not associated with endoscopic or symptomatic gastritis. Only -induced endoscopic gastritis requires gastric cancer surveillance. Owing to the weak correlation with , symptomatic gastritis should be assessed separately from histological and endoscopic gastritis.
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http://dx.doi.org/10.3390/jcm8030312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462939PMC
March 2019

Centrosome Linker-induced Tetraploid Segregation Errors Link Rhabdoid Phenotypes and Lethal Colorectal Cancers.

Mol Cancer Res 2018 09 21;16(9):1385-1395. Epub 2018 May 21.

Department of Sciences and Technologies, University of Sannio, Benevento, Italy.

Centrosome anomalies contribute to tumorigenesis, but it remains unclear how they are generated in lethal cancer phenotypes. Here, it is demonstrated that human microsatellite instable (MSI) and BRAF-mutant colorectal cancers with a lethal rhabdoid phenotype are characterized by inactivation of centrosomal functions. A splice site mutation that causes an unbalanced dosage of rootletin (CROCC), a centrosome linker component required for centrosome cohesion and separation at the chromosome 1p36.13 locus, resulted in abnormally shaped centrosomes in rhabdoid cells from human colon tissues. Notably, deleterious deletions at 1p36.13 were recurrent in a subgroup of BRAF-mutant and microsatellite stable (MSS) rhabdoid colorectal cancers, but not in classical colorectal cancer or pediatric rhabdoid tumors. Interfering with expression in near-diploid BRAF-mutant/MSI colon cancer cells disrupts bipolar mitotic spindle architecture, promotes tetraploid segregation errors, resulting in a highly aggressive rhabdoid-like phenotype Restoring near-wild-type levels of in a metastatic model harboring 1p36.13 deletion results in correction of centrosome segregation errors and cell death, revealing a mechanism of tolerance to mitotic errors and tetraploidization promoted by deleterious 1p36.13 loss. Accordingly, cancer cells lacking 1p36.13 display far greater sensitivity to centrosome spindle pole stabilizing agents These data shed light on a previously unknown link between centrosome cohesion defects and lethal cancer phenotypes providing new insight into pathways underlying genome instability. Mis-segregation of chromosomes is a prominent feature of chromosome instability and intratumoral heterogeneity recurrent in metastatic tumors for which the molecular basis is unknown. This study provides insight into the mechanism by which defects in rootletin, a centrosome linker component causes tetraploid segregation errors and phenotypic transition to a clinically devastating form of malignant rhabdoid tumor. .
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http://dx.doi.org/10.1158/1541-7786.MCR-18-0062DOI Listing
September 2018

[Identification of Nodular Gastritis among Patients Diagnosed with Lymphofollicular Gastritis on a Gastric Biopsied Specimen].

Korean J Gastroenterol 2018 03;71(3):143-152

Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.

Background/aims: Nodular gastritis (NG) is a well-known endoscopic finding observed in patients with a infection, which may lead to invasive gastric cancer. Lymphofollicular gastritis consists of lymphoid follicles or lymphoid cell aggregates, and is common in children. The aim of this study was to identify patients with NG from those in whom gastric biopsied specimens showed lymphoid follicles and lymphoid cell aggregates.

Methods: Subjects, whose gastric biopsy specimens showed lymphoid follicles or lymphoid cell aggregates, were included in this study. The inclusion criterion was that they underwent a serum pepsinogen assay on the day of upper gastrointestinal endoscopy. NG was diagnosed if the endoscopy findings revealed regular-sized, multiple, colorless subepithelial nodules.

Results: Among 108 subjects who showed lymphoid follicles or lymphoid cell aggregates, 13 (12.0%) revealed NG on endoscopy, and all these subjects showed positive Giemsa staining. Patients diagnosed with NG were younger (p=0.012) and showed a female predominance (p=0.001) compared to those without NG. The mean serum pepsinogen levels were higher (p=0.001) and lymphoid follicle-dominant subjects were more common (p<0.001) in the NG subjects than in those without NG. Logistic regression analysis revealed a younger age (p=0.041) and female gender (p=0.002) to be significant independent risk factors for NG.

Conclusions: NG should be distinguished from lymphofollicular gastritis because only 12% of patients showing gastric biopsy findings of lymphoid follicles and lymphoid cell aggregates demonstrated NG on endoscopy. NG is an endoscopic finding that is more common in women and in the younger population, irrespective of the biopsy findings and gastric secretory ability.
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http://dx.doi.org/10.4166/kjg.2018.71.3.143DOI Listing
March 2018

The histologic detection of Helicobacter pylori in seropositive subjects is affected by pathology and secretory ability of the stomach.

Helicobacter 2018 Jun 8;23(3):e12480. Epub 2018 Mar 8.

Departments of Pathology, Konkuk University School of Medicine, Seoul, Korea.

Background: Helicobacter pylori is unevenly distributed in hypochlorhydric environments. The study aim was to elucidate the risk factors for a negative Giemsa staining finding in seropositive subjects by measuring the secretory ability of the stomach.

Methods: Subjects aged over 18 years were included consecutively after endoscopic biopsy at gastric lesions with color or structural changes. Blood was sampled for the serum pepsinogen (PG) assay and H. pylori serology test. After excluding the subjects with past H. pylori eradication, the risk factors for a negative Giemsa staining finding in seropositive subjects were analyzed.

Results: Among 872 included subjects, a discrepancy between the serum anti-H. pylori IgG and Giemsa staining findings was found in 158 (18.1%) subjects, including 145 Giemsa-negative, seropositive subjects. Gastric adenocarcinoma/adenoma (OR = 11.090, 95% CI = 3.490-35.236) and low serum PG II level (OR = 0.931, 95% CI = 0.899-0.963) were the independent risk factors for a negative Giemsa staining finding in seropositive subjects. The cutoff value of serum PG II level was 7.45 ng/mL (area under curve [AUC] = 0.904, 95% CI = 0.881-0.927). Follow-up studies of Giemsa staining at different sites of the stomach revealed that 75% of the Giemsa-negative seropositive subjects with adenocarcinoma are positive, whereas none of those with low serum PG II level of <7.45 ng/mL revealed positive findings.

Conclusions: The risk of a negative Giemsa staining finding in seropositive subjects is increased in gastric adenocarcinoma/adenoma specimens and in subjects with a diminished gastric secretory ability with low serum PG II level of <7.45 ng/mL. A false-negative Giemsa staining finding is common in subjects with adenocarcinoma, and therefore, additional biopsies at different sites should be performed in these subjects.
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http://dx.doi.org/10.1111/hel.12480DOI Listing
June 2018

External Validation of a Gastric Cancer Nomogram Derived from a Large-volume Center Using Dataset from a Medium-volume Center.

J Gastric Cancer 2017 Sep 31;17(3):204-211. Epub 2017 Jul 31.

Department of Surgery, Konkuk University Medical Center, Seoul, Korea.

Purpose: Recently, a nomogram predicting overall survival after gastric resection was developed and externally validated in Korea and Japan. However, this gastric cancer nomogram is derived from large-volume centers, and the applicability of the nomogram in smaller centers must be proven. The purpose of this study is to externally validate the gastric cancer nomogram using a dataset from a medium-volume center in Korea.

Materials And Methods: We retrospectively analyzed 610 patients who underwent radical gastrectomy for gastric cancer from August 1, 2005 to December 31, 2011. Age, sex, number of metastatic lymph nodes (LNs), number of examined LNs, depth of invasion, and location of the tumor were investigated as variables for validation of the nomogram. Both discrimination and calibration of the nomogram were evaluated.

Results: The discrimination was evaluated using Harrell's C-index. The Harrell's C-index was 0.83 and the discrimination of the gastric cancer nomogram was appropriate. Regarding calibration, the 95% confidence interval of predicted survival appeared to be on the ideal reference line except in the poorest survival group. However, we observed a tendency for actual survival to be constantly higher than predicted survival in this cohort.

Conclusions: Although the discrimination power was good, actual survival was slightly higher than that predicted by the nomogram. This phenomenon might be explained by elongated life span in the recent patient cohort due to advances in adjuvant chemotherapy and improved nutritional status. Future gastric cancer nomograms should consider elongated life span with the passage of time.
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http://dx.doi.org/10.5230/jgc.2017.17.e21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620089PMC
September 2017

Diagnostic Limitation of Fine-Needle Aspiration (FNA) on Indeterminate Thyroid Nodules Can Be Partially Overcome by Preoperative Molecular Analysis: Assessment of RET/PTC1 Rearrangement in BRAF and RAS Wild-Type Routine Air-Dried FNA Specimens.

Int J Mol Sci 2017 Apr 12;18(4). Epub 2017 Apr 12.

Department of Surgery, Konkuk University School of Medicine, Seoul KS013, Korea.

Molecular markers are helpful diagnostic tools, particularly for cytologically indeterminate thyroid nodules. Preoperative rearrangement analysis in and wild-type indeterminate thyroid nodules would permit the formulation of an unambiguous surgical plan. Cycle threshold values according to the cell count for detection of the rearrangement by real-time reverse transcription-polymerase chain reaction (RT-PCR) using fresh and routine air-dried TPC1 cells were evaluated. The correlation of rearrangement between fine-needle aspiration (FNA) and paired formalin-fixed paraffin-embedded (FFPE) specimens was analyzed. rearrangements of 76 resected and wild-type classical PTCs were also analyzed. Results of RT-PCR and the Nanostring were compared. When 100 fresh and air-dried TPC1 cells were used, expression of rearrangement was detectable after 35 and 33 PCR cycles, respectively. The results of rearrangement in 10 FNA and paired FFPE papillary thyroid carcinoma (PTC) specimens showed complete correlation. Twenty-nine (38.2%) of 76 and wild-type classical PTCs had rearrangement. Comparison of rearrangement analysis between RT-PCR and the Nanostring showed moderate agreement with a κ value of 0.56 ( = 0.002). The rearrangement analysis by RT-PCR using routine air-dried FNA specimen was confirmed to be technically applicable. A significant proportion (38.2%) of the and wild-type PTCs harbored rearrangements.
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http://dx.doi.org/10.3390/ijms18040806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412390PMC
April 2017

Molecular Profiling of Papillary Thyroid Carcinoma in Korea with a High Prevalence of BRAF Mutation.

Thyroid 2017 06 21;27(6):802-810. Epub 2017 Apr 21.

4 Department of Internal Medicine, Konkuk University School of Medicine , Seoul, Korea.

Background: The BRAF mutation in papillary thyroid carcinoma (PTC) is particularly prevalent in Korea, and a considerable number of wild-type BRAF PTCs harbor RAS mutations. In addition, subsets of other genetic alterations clearly exist, but their prevalence in the Korean population has not been well studied. Recent increased insight into noninvasive encapsulated follicular variant PTC has prompted endocrine pathologists to reclassify this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). This study analyzed the genetic alterations among the histologic variants of PTC, including NIFTP.

Methods: Mutations of the BRAF and RAS genes and rearrangement of the RET/PTC1, NTRK1, and ALK genes using 769 preoperative fine-needle aspiration specimens and resected PTCs were analyzed.

Results: Molecular alterations were found in 687 (89.3%) of 769 PTCs. BRAF mutation (80.8%) was the most frequent alteration, followed by RAS mutation and RET/PTC1, NTRK1, and ALK rearrangements (5.6%, 2.1%, 0.4%, and 0%, respectively). The low prevalence of NTRK1 fusions and the absence of an ALK fusion detected in Korea may also be attributed to the higher prevalence of the BRAF mutation. There were significant differences in the frequency of the genetic alterations among the histologic variants of PTC. The prevalence of NIFTP in PTC was 2.7%, and among the NIFTPs, 28.6% and 57.1% harbored BRAF and RAS mutations, respectively. Clinicopathologic factors and mutational profiles between NIFTP and encapsulated follicular variant PTC with capsular invasion group were not significantly different.

Conclusions: Genetic alterations in PTC vary among its different histologic variants and seem to be different in each ethnic group.
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http://dx.doi.org/10.1089/thy.2016.0547DOI Listing
June 2017

Molecular Testing for Gastrointestinal Cancer.

J Pathol Transl Med 2017 Mar 19;51(2):103-121. Epub 2017 Feb 19.

Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype ( and exon 2-4). A mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 () and is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the mutation is a prognostic biomarker and the mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, silver or fluorescence hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus-positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.
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http://dx.doi.org/10.4132/jptm.2017.01.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357760PMC
March 2017

Discovery of gastric cancer specific biomarkers by the application of serum proteomics.

Proteomics 2017 03;17(6)

Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yong-in City, Republic of Korea.

Current diagnostic markers for gastric cancer are not sufficiently specific or sensitive for use in clinical practice. The aims of this study are to compare the proteomes of serum samples from patients with gastric cancers and normal controls, and to develop useful tumor markers of gastric cancer by quantitative proteomic analysis. We identified a total of 388 proteins with a ≤1% FDR and with at least two unique peptides from the sera of each group. Among them, 215, 251, and 260 proteins were identified in serum samples of patients in an advanced cancer group, early cancer group, and normal control group, respectively. We selected differentially expressed proteins in cancer patients compared with those of normal controls via semiquantitative analyses comparing the spectral counts of identified proteins. These differentially expressed proteins were successfully verified using an MS-based quantitative assay, multiple reactions monitoring analysis. Four proteins (vitronectin, clusterin isoform 1, thrombospondin 1, and tyrosine-protein kinase SRMS) were shown to have significant changes between the cancer groups and the normal control group. These four serum proteins were able to discriminate gastric cancer patients from normal controls with sufficient specificity and selectivity.
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http://dx.doi.org/10.1002/pmic.201600332DOI Listing
March 2017

Differences in Prevalence of Lymphovascular Invasion among Early Gastric Cancers between Korea and Japan.

Gut Liver 2017 May;11(3):383-391

Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background/aims: The presence of invasion is a diagnostic criterion of early gastric cancer (EGC) in Korea, whereas diagnosis in Japan is based on enlarged nuclei and prominent nucleoli. Moreover, the depth of invasion is the location of cancer cell infiltration in Korea, whereas it is the location of lymphovascular invasion (LVI) or cancer cell infiltration in Japan. We evaluated the characteristics of EGC with LVI to uncover the effects of different diagnostic criteria.

Methods: Consecutive T1-stage EGC patients who underwent complete resection were included after endoscopic or surgical resection. The presence of LVI was evaluated.

Results: LVI was present in 112 of 1,089 T1-stage EGC patients. LVI was associated with depth of invasion (p<0.001) and age (p=0.017). The prevalence of LVI in mucosal cancer was significantly higher in Korea (p<0.001), whereas that of submucosal cancer was higher in Japan (p=0.024). For mucosal EGC types, LVI was positively correlated with diagnostic criteria applied in Korea (p=0.017). For submucosal EGC types, LVI was positively correlated with Japanese criteria (p=0.001) and old age (p=0.045).

Conclusions: The higher prevalence of LVI for mucosal EGC in Korea and for submucosal EGC in Japan indicates that different diagnostic criteria should be considered when reading publications from other countries.
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http://dx.doi.org/10.5009/gnl16281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417781PMC
May 2017

Use of Omega-3 Polyunsaturated Fatty Acids to Treat Inspissated Bile Syndrome: A Case Report.

Pediatr Gastroenterol Hepatol Nutr 2016 Dec 28;19(4):286-290. Epub 2016 Dec 28.

Department of Pediatrics, Konkuk University Medical Center, Seoul, Korea.

Inspissated bile syndrome (IBS) is a rare condition in which thick intraluminal bile, including bile plugs, sludge, or stones, blocks the extrahepatic bile ducts in an infant. A 5-week-old female infant was admitted for evaluation of jaundice and acholic stool. Diagnostic tests, including ultrasound sonography, magnetic resonance cholangiopancreatography, and a hepatobiliary scan, were not conclusive. Although the diagnosis was unclear, the clinical and laboratory findings improved gradually on administration of urodeoxycholic acid and lipid emulsion containing omega-3 polyunsaturated fatty acids (PUFAs) for 3 weeks. However, a liver biopsy was suggestive of biliary atresia. This finding forced us to perform intraoperative cholangiography, which revealed a patent common bile duct with impacted thick bile. We performed normal saline irrigation and the symptom was improved, the final diagnosis was IBS. Thus, we herein report that IBS can be treated with omega-3 PUFAs as an alternative to surgical intervention.
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http://dx.doi.org/10.5223/pghn.2016.19.4.286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234414PMC
December 2016

BRAF-Mutated Colorectal Cancer Exhibits Distinct Clinicopathological Features from Wild-Type BRAF-Expressing Cancer Independent of the Microsatellite Instability Status.

J Korean Med Sci 2017 Jan;32(1):38-46

Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.

In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.
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http://dx.doi.org/10.3346/jkms.2017.32.1.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143296PMC
January 2017

Nodule Regression in Adults With Nodular Gastritis.

Gastroenterology Res 2015 Dec 31;8(6):296-302. Epub 2015 Dec 31.

Department of Pathology, Konkuk University School of Medicine, Seoul, Korea.

Background: Nodular gastritis (NG) is associated with the presence of infection, but there are controversies on nodule regression in adults. The aim of this study was to analyze the factors that are related to the nodule regression in adults diagnosed as NG.

Methods: Adult population who were diagnosed as NG with infection during esophagogastroduodenoscopy (EGD) at our center were included. Changes in the size and location of the nodules, status of infection, upper gastrointestinal (UGI) symptom, EGD and pathology findings were analyzed between the initial and follow-up tests.

Results: Of the 117 NG patients, 66.7% (12/18) of the eradicated NG patients showed nodule regression after eradication, whereas 9.9% (9/99) of the non-eradicated NG patients showed spontaneous nodule regression without eradication (P < 0.001). Nodule regression was more frequent in NG patients with antral nodule location (P = 0.010), small-sized nodules (P = 0.029), eradication (P < 0.001), UGI symptom (P = 0.007), and a long-term follow-up period (P = 0.030). On the logistic regression analysis, nodule regression was inversely correlated with the persistent infection on the follow-up test (odds ratio (OR): 0.020, 95% confidence interval (CI): 0.003 - 0.137, P < 0.001) and short-term follow-up period < 30.5 months (OR: 0.140, 95% CI: 0.028 - 0.700, P = 0.017).

Conclusions: In adults with NG, eradication is the most significant factor associated with nodule regression. Long-term follow-up period is also correlated with nodule regression, but is less significant than eradication. Our findings suggest that eradication should be considered to promote nodule regression in NG patients with infection.
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http://dx.doi.org/10.14740/gr692wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051029PMC
December 2015

Frequent somatic TERT promoter mutations and CTNNB1 mutations in hepatocellular carcinoma.

Oncotarget 2016 Oct;7(43):69267-69275

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma.
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http://dx.doi.org/10.18632/oncotarget.12121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342476PMC
October 2016

Inverse Correlation between Cancer Size and Abdominal Obesity in Colorectal Cancer Cases.

Asian Pac J Cancer Prev 2016 ;17(8):4025-30

Departments of Internal Medicine, Radiology, Pathology, and Surgery, Konkuk University School of Medicine, Seoul, Korea E-mail :

Background: Correlation between colorectal cancer (CRC) and abdominal obesity has been established, but there is a paucity of data on non-obese CRC patients. The aim of this study was to establish the characteristics of CRCs that occur in such patients.

Materials And Methods: Consecutive CRC patients without cachexia were included. Unintended body weight loss, T4- or M1-staged CRCs, extensive lymph node involvement, or synchronous malignancy were classified as cachectic conditions. Abdominal fat volumes were measured using a multidetector CT unit with software (Rapidia, INFINITT, Seoul, Korea).

Results: Of the newly-diagnosed CRC patients, 258 non-cachectic and 88 cachectic patients were analyzed. The cancer size (p<0.001) and T stage (p<0.001) were inversely correlated with body mass index (BMI), visceral fat and subcutaneous fat volumes. Cancer size was the only independent factor related to BMI (p=0.016), visceral fat volume (p=0.002), and subcutaneous fat volume (p=0.027). In non-cachectic patients, a significant inverse correlation was found only between the cancer size and visceral fat volume (p=0.017).

Conclusions: Non-obese CRC patients tend to have larger CRC lesions than their obese counterparts even under non-cachectic conditions. Such an inverse correlation between cancer size and visceral fat volume suggests that considerable CRCs are not correlated with abdominal obesity.
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February 2017

Does the antibody production ability affect the serum anti-Helicobacter pylori IgG titer?

World J Gastrointest Pathophysiol 2016 Aug;7(3):288-95

Hyun Ah Chung, Sun-Young Lee, Jeong Hwan Kim, In-Kyung Sung, Hyung Seok Park, Chan Sup Shim, Department of Internal Medicine, Konkuk University School of Medicine, Seoul 05030, South Korea.

Aim: To investigate the relationship between serum titers of anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG) and hepatitis B virus surface antibody (HBsAb).

Methods: Korean adults were included whose samples had positive Giemsa staining on endoscopic biopsy and were studied in the hepatitis B virus surface antigen (HBsAg)/HBsAb serologic assay, pepsinogen (PG) assay, and H. pylori serologic test on the same day. Subjects were excluded if they were positive for HBsAg, had a recent history of medication, or had other medical condition(s). We analyzed the effects of the following factors on serum titers of HBsAb and the anti-H. pylori IgG: Age, density of H. pylori infiltration in biopsy samples, serum concentrations of PG I and PG II, PG I/II ratio, and white blood cell count.

Results: Of 111 included subjects, 74 (66.7%) exhibited a positive HBsAb finding. The serum anti-H. pylori IgG titer did not correlate with the serum HBsAb titer (P = 0.185); however, it correlated with the degree of H. pylori infiltration on gastric biopsy (P < 0.001) and serum PG II concentration (P = 0.042). According to the density of H. pylori infiltration on gastric biopsy, subjects could be subdivided into those with a marked (median: 3.95, range 0.82-4.00) (P = 0.458), moderate (median: 3.37, range 1.86-4.00), and mild H. pylori infiltrations (median: 2.39, range 0.36-4.00) (P < 0.001). Subjects with a marked H. pylori infiltration on gastric biopsy had the highest serological titer, whereas in subjects with moderate and mild H. pylori infiltrations titers were correspondingly lower (P < 0.001). After the successful eradication, significant decreases of the degree of H. pylori infiltration (P < 0.001), serum anti-H. pylori IgG titer (P < 0.001), and serum concentrations of PG I (P = 0.028) and PG II (P = 0.028) were observed.

Conclusion: The anti-H. pylori IgG assay can be used to estimate the burden of bacteria in immunocompetent hosts with H. pylori infection, regardless of the HBsAb titer after HBV vaccination.
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http://dx.doi.org/10.4291/wjgp.v7.i3.288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981769PMC
August 2016

Fibrosis Within the Tympanic Membrane.

J Craniofac Surg 2016 Jul;27(5):e427-8

*Department of Otorhinolaryngology-Head and Neck Surgery†Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea.

A primary mass lesion arising from the tympanic membrane is extremely rare. The authors report a patient of extensive fibrosis within the tympanic membrane in a 65-year-old woman who did not have a history of ear infection. The patient complained of slow progressing hearing loss on the left side without otorrhea or otalgia. Otoscopic examination showed a thick tympanic membrane with whitish mass-like bulge, and pure-tone audiometry revealed conductive hearing loss. The lesion was totally resected, and final findings of a histopathologic examination revealed extensive fibrosis with subsiding inflammation within the tympanic membrane. Fibrosis within the tympanic membrane may present with slow progressing conductive hearing loss and should be considered a possible differential diagnosis of mass lesions in the tympanic membrane.
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http://dx.doi.org/10.1097/SCS.0000000000002703DOI Listing
July 2016

Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma.

J Korean Med Sci 2016 Jun 11;31(6):866-72. Epub 2016 Apr 11.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea .

Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005-2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.
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http://dx.doi.org/10.3346/jkms.2016.31.6.866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853664PMC
June 2016

Prognostic Significance of TERT Promoter Mutations in Papillary Thyroid Carcinomas in a BRAF(V600E) Mutation-Prevalent Population.

Thyroid 2016 07 6;26(7):901-10. Epub 2016 Jun 6.

3 Department of Surgery, Konkuk University School of Medicine , Seoul, Korea.

Background: The role of telomerase reverse transcriptase (TERT) promoter mutations in differentiated thyroid cancer has been well established. These mutations have a significantly higher prevalence in aggressive thyroid tumors, including widely invasive oncocytic carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas. Interestingly, in some studies, TERT mutations were found to be more common in tumors with a BRAF(V600E) mutation. However, mutational analysis of TERT promoter mutations in thyroid tumors has not been previously performed for patients in Korea, where the BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is particularly prevalent. This study analyzed TERT promoter mutations in various thyroid tumors and examined their relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases.

Methods: Using 242 preoperative fine-needle aspiration biopsy specimens (including 207 PTCs) with confirmed histopathological diagnosis of the biopsied thyroid nodules, the TERT promoter status (C228T and C250T) was analyzed, and the relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases was examined.

Results: Of 242 patients, 14.5% (30/207), 26.7% (4/15), 50% (1/2), and 60% (2/5) of PTCs, follicular thyroid carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas harbored a TERT(C228T) mutation, respectively. The TERT(C228T) mutation was associated with recurrence (p = 0.03). However, no association with other clinicopathologic factors in PTC was found. Coexistence of TERT(C228T) and BRAF(V600E) mutations was found in 13.0% of PTCs and was significantly associated with older age and advanced stage compared with the group negative for either mutation. The TERT(C228T) mutation status was an independent prognostic factor for recurrence-free survival (hazard ratio = 3.08 [confidence interval 1.042-9.079]; p = 0.042) in patients with PTC in multivariate analysis.

Conclusions: Identification of TERT promoter mutations in preoperative fine-needle aspiration biopsy specimens may help in better characterizing the prognosis and triaging thyroid cancer patients for appropriate treatment.
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http://dx.doi.org/10.1089/thy.2015.0488DOI Listing
July 2016
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