Publications by authors named "Soo Kee Min"

55 Publications

Erratum to "BRAF and NRAS mutations and antitumor immunity in Korean malignant melanomas and their prognostic relevance: Gene set enrichment analysis and CIBERSORT analysis" [Pathol. Res. Pract. 215 (12) (2019) 152671].

Pathol Res Pract 2021 Mar 19;219:153316. Epub 2021 Feb 19.

Department of Hematological Oncology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14068, Republic of Korea.

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http://dx.doi.org/10.1016/j.prp.2020.153316DOI Listing
March 2021

Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma.

Diagn Pathol 2020 Oct 14;15(1):126. Epub 2020 Oct 14.

Department of Pathology, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea.

Background: Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC.

Methods: We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers.

Results: PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002).

Conclusions: PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.
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http://dx.doi.org/10.1186/s13000-020-01045-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557072PMC
October 2020

Comparative pathologic analysis of mediastinal B-cell lymphomas: selective expression of p63 but no GATA3 optimally differentiates primary mediastinal large B-cell lymphoma from classic Hodgkin lymphoma.

Diagn Pathol 2019 Dec 12;14(1):133. Epub 2019 Dec 12.

Department of Pathology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea.

Background: Interpretation of mediastinal biopsy is often challenging even for experienced pathologists especially when a hematolymphoid neoplasm is suspected. Primary mediastinal large B-cell lymphoma (PMLBCL) and classic Hodgkin lymphoma (CHL) represent two major types of mature B-cell lymphomas of the mediastinum. Although PMLBCL and mediastinal CHL share many clinicopathologic characteristics, their treatment strategies and responses are remarkably different. We therefore aimed to find distinctive histologic or protein markers to better differentiate these two lesions.

Methods: Search for primary mediastinal B-cell lymphomas found 52 consecutive cases from 3 university hospitals of Korea during 2005 to 2012. Among them, 32 cases that were available for additional immunohistochemistry (IHC) assessment were enrolled in this study. These cases consisted of the following: CHL (N = 13), PMLBCL (N = 16), and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (gray zone lymphoma, N = 3). Along with the clinicopathologic findings, the expression of p63, GATA3 and cyclin E was investigated by IHC in the three categorized lesions mentioned above.

Results: Most clinical features overlapped between PMLBCL and CHL except for the increased disease progression and mortality found in PMLBCL. In the pathologic review, the presence of epithelioid granuloma favored a diagnosis of CHL, whereas reticulated or alveolar patterns of fibrosis were characteristic of PMLBCL. For protein markers, p63 was predominantly positive in PMLBCL (15/16) compared with CHL (2/13), which indicates that p63 is a marker of the highest diagnostic accuracy when calculated by the area under the ROC curve. GATA3 was expressed in the majority of CHL cases (10/13) compared with PMLBCL (0/16), while the expression of cyclin E was only rarely present in a minor population of PMLBCL.

Conclusions: P63 expression in tumor cells, even focal expression, and no GATA3 is the most helpful feature in distinguishing PMLBCL from mediastinal CHL.
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http://dx.doi.org/10.1186/s13000-019-0918-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909622PMC
December 2019

BRAF and NRAS mutations and antitumor immunity in Korean malignant melanomas and their prognostic relevance: Gene set enrichment analysis and CIBERSORT analysis.

Pathol Res Pract 2019 Dec 27;215(12):152671. Epub 2019 Sep 27.

Department of Hematological Oncology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 14068, Republic of Korea.

Cutaneous malignant melanomas (CMMs) are rare but are the cause of the highest skin cancer-related mortality in Korea. Very few studies have investigated the associations between KRAS, NRAS, BRAF, and PIK3CA mutations and TICs, as well as their prognostic impact on Korean CMMs. Peptide nucleic acid-mediated polymerase chain reaction clamping and Mutyper and immunohistochemistry were used to detect these mutations in 47 paraffinized CMMs. BRAF and NRAS mutations were detected in 21.3% and 12.8% of CMMs, respectively. No KRAS or PIK3CA mutations were identified. NRAS mutations correlated with low FOXP3 (regulatory T lymphocyte marker) and indoleamine 2,3-dioxygenase (IDO) (activated dendritic cell marker) TICs in CMMs, which is consistent with the negative correlation of regulatory T cells with NRAS mutations in TCGA data, while BRAF mutations were not associated with any TICs. In gene set enrichment analysis, BRAF and NRAS mutations were enriched in decreased CD8 (suppressor/cytotoxic T lymphocyte marker) T cell-linked and increased CD4 (helper/inducer T lymphocyte marker) T cell-linked gene signatures, respectively, confirming the trend in our cohort of associations only with NRAS. BRAF or NRAS mutations alone did not affect any prognosis. In the subgroup analyses, BRAF mutations, as well as high CD4, CD8, FOXP3, and IDO TICs, caused worse overall survival in NRAS-mutated melanoma. No correlation of CD163 (monocyte-macrophage-specific marker) was detected. We found that approximately one-third of our cohort had BRAF and NRAS mutations, none had KRAS or PIK3CA mutations, and most displayed decreased anti-tumor immunity. These findings may warrant further study on combined immunotherapeutic and molecular targeted therapy in Korean CMMs. Subgroup analyses according to TICs and BRAF/NRAS mutations may help to identify high-risk patients with worse prognoses.
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http://dx.doi.org/10.1016/j.prp.2019.152671DOI Listing
December 2019

Targeted next-generation sequencing of well-differentiated rectal, gastric, and appendiceal neuroendocrine tumors to identify potential targets.

Hum Pathol 2019 05 6;87:83-94. Epub 2019 Mar 6.

Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, Republic of Korea.

Rectal neuroendocrine tumors (NETs) are the most common gastrointestinal (GI) NETs with an uncertain malignant potential despite their small size. There are limited data about driver mutations in rectal NETs, which may explain the tumors' unexpected behavior or common histologic morphology with other GI-NETs. Here, we investigated the clinically and pathologically relevant mutations of rectal and nonrectal NETs and compared the frequency and clinical significance of detected mutations between them. We sequenced 84 primary GI-NETs (69 rectal, 7 gastric, 5 appendiceal, and 3 sigmoid colon NETs) and 3 metastatic GI-NETs using targeted next-generation sequencing. Twenty-one rectal NETs (30.4%) showed at least 1 mutation in 24 cancer-related genes; the most common mutations were TP53 (10.1%) and FBXW7 (7.2%), of which 73% were pathogenic/likely pathogenic mutations. TP53 (p.R337C and p.R213*), PTEN (p.W111*, p.Q214*), CDKN2A (p.W110*), FBXW7 (p.R465H), and AKT1 (p.R23Q) were repetitive mutations found exclusively in rectal NETs, whereas SMAD4 (p.R361C) and STK11 (p.D176N) were repetitive mutations found only in gastric NETs. PTEN (p.G129K), EGFR (p.E709K), and KIT (p.V555I) were shared mutations between rectal and appendiceal NETs, whereas SMAD4 (p.R361C), ALK (p.G1202R), VHL (p.Q132*), and IDH1 (p.R132H) were concurrently detected between rectal and gastric NETs. GI-NETs with higher histologic grades, lymphovascular invasion, or recurrence tended to have higher numbers of mutation variants than other tumors; however, there was no significant difference. In conclusion, rectal NETs commonly carried pathogenic/likely pathogenic mutations. Because most mutations were identified in nonhotspot positions, next-generation sequencing is useful in identifying potential drug targets in rectal NETs.
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http://dx.doi.org/10.1016/j.humpath.2019.02.007DOI Listing
May 2019

Treatment for gastric 'indefinite for neoplasm/dysplasia' lesions based on predictive factors.

World J Gastroenterol 2019 Jan;25(4):469-484

Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, South Korea.

Background: Gastric 'indefinite for neoplasm/dysplasia' (IFND) is a borderline lesion that is difficult to diagnose as either regenerative or neoplastic. There is a need for guidance in the identification of a subset of patients, who have an IFND lesion with a higher risk of malignant potential, to enable risk stratification and optimal management.

Aim: To determine the clinical and pathologic factors for the accurate diagnosis of gastric IFND lesions.

Methods: In total, 461 gastric lesions diagnosed biopsy as IFND lesions were retrospectively evaluated. Endoscopic resection ( = 134), surgery ( = 22), and follow-up endoscopic biopsy ( = 305) were performed to confirm the diagnosis. The time interval from initial biopsy to cancer diagnosis was measured, and diagnostic delays were categorized as > 2 wk, > 2 mo, > 6 mo, and > 1 year. The IFND lesions presenting as regenerating atypia (60%) or atypical epithelia (40%) at initial biopsy were adenocarcinomas in 22.6%, adenomas in 8.9%, and gastritis in 68.5% of the cases.

Results: Four clinical factors [age ≥ 60 years (2.445, 95%CI: 1.305-4.580, = 0.005), endoscopic size ≥ 10 mm (3.519, 95%CI: 1.891-6.548, < 0.001), single lesion (5.702, 95%CI: 2.212-14.696, < 0.001), and spontaneous bleeding (4.056, 95%CI: 1.792-9.180, = 0.001)], and two pathologic factors [atypical epithelium (25.575, 95%CI: 11.537-56.695, < 0.001], and repeated IFND diagnosis [6.022, 95%CI: 1.822-19.909, = 0.003)] were independent risk factors for gastric cancer. With two or more clinical factors, the sensitivity and specificity for carcinoma were 91.3% and 54.9%, respectively. Ten undifferentiated carcinomas were initially diagnosed as IFND. In the subgroup analysis, fold change (5.594, 95%CI: 1.458-21.462, = 0.012) predicted undifferentiated or invasive carcinoma in the submucosal layers or deeper. Diagnostic delays shorter than 1 year were not associated with worse prognoses. Extremely well-differentiated adenocarcinomas accounted for half of the repeated IFND cases and resulted in low diagnostic accuracy even on retrospective blinded review.

Conclusion: More than two clinical and pathologic factors each had significant cut-off values for gastric carcinoma diagnosis; in such cases, endoscopic resection should be considered.
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http://dx.doi.org/10.3748/wjg.v25.i4.469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350171PMC
January 2019

Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in ALK-positive lung cancer: Comparison with EGFR-mutated lung cancer.

Pathol Res Pract 2019 Mar 10;215(3):459-465. Epub 2018 Dec 10.

Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Kyoungchun-ro 153, Guri-si, Gyeonggi-do, 11923, Republic of Korea.

ALK-positive (ALK+) lung adenocarcinoma usually shows a more advanced-staged disease with frequent nodal metastasis and highly aggressive outcomes compared with EGFR-mutated lung cancers. The aim of this study was to investigate the expression profiles of several mucins in ALK + lung cancers to gain insight into the relationship between the more aggressive biological nature of ALK + lung cancers and the role of mucins. We examined the immunohistochemical profiles of mucins MUC1, MUC2, MUC5AC, and MUC6 in 19 ALK + lung cancers compared with 42 EGFR-mutated lung cancers. ALK + cancers were found to occur in younger patients and were characterized by a solid-predominant histologic subtype with frequent signet ring cells and peritumoral muciphages. By contrast, EGFR-mutated cancers lacked ALK-specific histological patterns. Although all MUC1 and MUC5AC were expressed in both subtypes, MUC1 expression in ALK + cancers was visualized exclusively through cytoplasmic staining, whereas those in EGFR-mutated cancers were predominantly membranous staining in apical area (92.9%) and focally in cytoplasmic staining (7.1%). MUC5AC expression in ALK + cancers was exclusively visualized through cytoplasmic staining (100%), whereas EGFR-mutated cancers showed predominantly perinuclear dot-like patterns (90.5%) and focal cytoplasmic staining (9.5%). MUC2 and MUC6 expression was not detected in either type of lung cancer. CONCLUSIONS: The high frequency of both MUC1 and MUC5AC cytoplasmic expression, coupled with a lack of MUC2 and MUC6 expression in ALK + lung cancer may contribute to the biologically aggressive behavior of ALK + cancer. Inhibitors to these types of mucins may thus act as a barrier to cancerous extension reducing their aggressive behavior.
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http://dx.doi.org/10.1016/j.prp.2018.12.011DOI Listing
March 2019

Gastric follicular lymphoma: A report of 3 cases and a review of the literature.

Oncol Lett 2018 Jul 18;16(1):741-748. Epub 2018 May 18.

Department of Pathology, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.

Follicular lymphoma (FL) occurs primarily in the gastrointestinal tract, with the stomach being one of the rarest sites. According to the literature, <20 cases of primary gastric FL have been reported, with the number of cases with detailed pathological descriptions being even less. The aim of the present study was to compare clinicopathological features of gastric FL with FL at alternative sites. A total of 3 cases of gastric FL were retrieved from among 3,216 cases in the databases of 4 university hospitals in South Korea: Seoul National University (SNU) Hospital, SNU Boramae Hospital, SNU Bundang Hospital (all Seoul, South Korea) and Dongtan Sacred Heart Hospital Hallym University (Dongtan, South Korea), including 2 primary cases and 1 case that was possibly secondary to nodal FL. The 2 primary gastric FL cases were incidentally detected in routine health check-ups. An endoscopy revealed a single polypoid submucosal mass and biopsies failed to confirm the diagnosis due to minimal mucosal involvement. Therefore, a partial gastrectomy was performed. The epicenters of the tumors were submucosal, with focal extension to the muscularis propria. However, 1 case exhibited an isolated FL nodule in the omentum. Histopathological examination revealed FL of grade 1-2 with a follicular pattern and with strong expression of germinal center markers and B-cell lymphoma 2 (BCL2). Rearrangement of BCL2 was not identified using fluorescence hybridization studies in 2 cases. In contrast to these 2 cases, the remaining FL case was confirmed with an endoscopic biopsy. The endoscopy revealed multiple eroded polypoid lesions, and pathology revealed FL of grade 1-2 with a predominantly diffuse pattern, and with immunoglobulin heavy chain IGH/BCL2 translocation. In view of the extensive lymphadenopathy, the last case possibly presented as secondary involvement of nodal FL. It is challenging to diagnose FL in the stomach due to little mucosal involvement, as well as the unfamiliarity of the tumor due to its rarity. However, the results of the present study suggest that primary gastric FL may exhibit unique pathological features, including a predominantly follicular pattern and an absence of BCL2 rearrangement.
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http://dx.doi.org/10.3892/ol.2018.8744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019973PMC
July 2018

Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors.

Biomed Res Int 2018 27;2018:1013640. Epub 2018 Mar 27.

Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 170beon-gil, 22 Gwanpyeong-ro, Dongan-gu, Anyang-si, Gyeonggi-do 14068, Republic of Korea.

Mitotic counts in the World Health Organization (WHO) grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs). The mitosis-specific marker phosphohistone H3 (PHH3) can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI) and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades.
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http://dx.doi.org/10.1155/2018/1013640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892266PMC
October 2018

Safety and feasibility of laparoscopic surgery for appendiceal mucocele: a multicenter study.

Surg Endosc 2018 11 13;32(11):4408-4414. Epub 2018 Apr 13.

Department of Surgery, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 40, Sukwoo-Dong, Hwaseong-Si, 445-170, Gyeonggi-Do, Republic of Korea.

Background: Although laparoscopic appendectomy has been widely performed since 1987, concerns over potential spillage of mucus into the peritoneal cavity during laparoscopic manipulation have prevented the use of laparoscopic surgery (LS) for appendiceal mucocele. The purpose of the present study was to evaluate the safety, feasibility, and short-term perioperative outcomes of LS for appendiceal mucocele.

Methods: A retrospective review was performed to identify patients diagnosed with appendiceal mucocele based on their imaging studies and who underwent surgery at one of six Hallym-University-affiliated hospitals between January 2007 and June 2016. Patient demographics, surgical outcomes, and postoperative outcomes were retrospectively analyzed.

Results: A total of 96 patients were evaluated, of whom 58 underwent LS (LS group) and 38 underwent open surgery (OS; OS group). There were no significant differences in patient characteristics between groups. The operation time was similar in both groups (P = 0.399). Intraoperative rupture occurred in two patients in each group (no significant difference, P = 0.647). Time to flatus, time to soft food intake, and length of hospital stay were shorter in the LS group than in the OS group (2.4 vs. 3.2 days, P = 0.003; 3.6 vs. 4.5 days, P = 0.024; 6.5 vs. 8.8 days, P = 0.011, respectively). The rate of postoperative complications was similar between the groups (P = 0.786). Univariate analysis revealed that rupture of appendiceal mucocele was associated with white blood cell count > 10,000/µL (P = 0.032) but not with LS (P = 0.647).

Conclusions: The results showed that LS is safe and feasible for the surgical treatment of appendiceal mucocele. An elevated WBC count was associated with a risk of appendiceal mucocele rupture.
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http://dx.doi.org/10.1007/s00464-018-6182-4DOI Listing
November 2018

Clinical implication of programmed cell death-1 ligand-1 expression in tonsillar squamous cell carcinoma in association with intratumoral heterogeneity, human papillomavirus, and epithelial-to-mesenchymal transition.

Hum Pathol 2018 10 7;80:28-39. Epub 2018 Apr 7.

Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri-si, Gyeonggi-do 11923, Republic of Korea.

Programmed cell death-1 ligand-1 (PD-L1), essential for immune evasion, is a potential candidate for pathogenesis and therapeutic target of human papillomavirus (HPV)-positive tonsillar squamous cell carcinomas (TSCCs). MET/hepatocyte growth factor signaling and transcription factors involved in epithelial-to-mesenchymal transition (EMT) upregulate PD-L1, which can contribute to clinical outcome. Intratumoral heterogeneity of PD-L1 expression is of clinical importance in selection bias due to false-negative patient enrollment. However, the clinicopathological features, prognostic value, and coexpressed molecules of PD-L1 remain unclear in TSCCs. PD-L1 expression was evaluated via immunohistochemistry using a specific monoclonal antibody (SP142) between whole-tissue and tissue microarray (TMA) sections of 79 tumors (5% cutoff value with weak staining). Expressions of EMT markers (TWIST1, Snail, and SNIP1) and MET/hepatocyte growth factor were also analyzed. Staining of the TMA sections showed 78.5% concordance rate to the whole section. PD-L1 positivity and its intratumoral heterogeneity were 29.1% and 15.2% of TSCCs by whole section, respectively. PD-L1 positivity was prevalent in females, HPV-positive tumors without base of tongue invasion, and SNIP1-overexpressed tumors. SNIP1 overexpression, unmethylated TWIST1, smoking, and poorly differentiated tumors were predictive for PD-L1 overexpression. PD-L1 positivity was a favorable independent prognostic factor. Subgroup analyses according to the coexpression of PD-L1 with HPV, SNIP1, or unmethylated TWIST1 indicated the best clinical outcome than any other subgroups. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequent, warranting a caution in punching TMA cores. A combined analysis of PD-L1 with EMT and HPV may define a characteristic subset of patients and prognostic group.
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http://dx.doi.org/10.1016/j.humpath.2018.03.025DOI Listing
October 2018

Differential diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoproliferative lesions: A report of three cases.

Blood Res 2017 Dec 26;52(4):326-329. Epub 2017 Dec 26.

Department of Pathology, Hallym University Sacred Heart Hospital, Seoul, Korea.

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http://dx.doi.org/10.5045/br.2017.52.4.326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762748PMC
December 2017

Ultrasound features of secondary appendicitis in pediatric patients.

Ultrasonography 2018 Jul 25;37(3):233-243. Epub 2017 Aug 25.

Department of Radiology, Hallym University Sacred Heart Hospital, Anyang, Korea.

Purpose: The purpose of this study was to evaluate the ultrasonographic findings of secondary appendicitis (SA) and to discuss the differential findings compared with primary appendicitis.

Methods: In this study, we analyzed the ultrasonographic findings of 94 patients under 15 years old of age treated at our institution from May 2005 to May 2014 who had bowel inflammation and an inflamed appendix with a maximal outer diameter >6 mm that improved with nonsurgical treatment (the SA group). Ninety-nine patients with pathologically proven acute appendicitis (the primary appendicitis [PA] group) from June 2013 to May 2014 and 44 patients with pathologically negative appendectomy results from May 2005 to May 2014 were also included to compare the ultrasonographic features of these conditions. A retrospective review of the ultrasonographic findings was performed by two radiologists. The clinical and laboratory findings were also reviewed. The results were statically analyzed using analysis of variance, the Pearson chi-square test, and the two-tailed Fisher exact test.

Results: Compared with PA, cases of SA had a smaller diameter (9.8 mm vs. 6.6 mm, P<0.001), and were less likely to show periappendiceal fat inflammation (98% vs. 6%, P<0.001) or an appendicolith (34% vs. 11%, P<0.001). SA showed mural hyperemia on color Doppler ultrasonography as frequently as PA (P=0.887).

Conclusion: The ultrasonographic features of SA included an increased diameter compared to a healthy appendix and the same level of hyperemia as in PA. However, the diameter was commonly in the equivocal range (mean diameter, 6.6 mm), and periappendiceal fat inflammation was rarely present in SA.
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http://dx.doi.org/10.14366/usg.17029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044217PMC
July 2018

Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection.

Oncotarget 2017 Oct 19;8(47):82399-82414. Epub 2017 Jul 19.

Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do 11923, Republic of Korea.

Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial. We performed hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers. A multiplex polymerase chain reaction with five quasimonomorphic markers was performed for MSI. PD-L1 expression was observed in 123 cases (31.2%), and clinicopathological features such as MET overexpression, high pT stage, and a lack of lymphatic invasion represent significant risk factors associated with PD-L1 overexpression in gastric cancers. No associations of EBV, MSI, or mucin phenotype with PD-L1 expression were statistically significant. PD-L1 expression was a strong indicator for worse overall survival (OS) but borderline significant in disease-free survival (DFS). A combined analysis of PD-L1 and MET expression indicated that the PD-L1+/MET+ subgroup showed the worst prognosis when compared to the PD-L1-/MET- subgroup, which had the best clinical outcome. Furthermore, PD-L1 overexpression exhibited poor prognosis in terms of both OS and DFS in EBV-negative, microsatellite stable, and intestinal mucin phenotype tumors. In conclusion, this is the first study to evaluate the overexpression of MET as a risk factor for PD-L1 positivity in gastric cancer tissue as well as the reliability and prognostic relevance of PD-L1/MET co-expression after surgery.
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http://dx.doi.org/10.18632/oncotarget.19390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669899PMC
October 2017

Mutation analysis of CTNNB1 gene and the ras pathway genes KRAS, NRAS, BRAF, and PIK3CA in eyelid sebaceous carcinomas.

Pathol Res Pract 2017 Jun 1;213(6):654-658. Epub 2017 Mar 1.

Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Gyeonggi-do 431-070, Republic of Korea.

Sebaceous carcinoma (SC) represents a rare, aggressive eyelid malignancy with poor prognosis and is a possible component of Muir-Torre syndrome. However, genetic features as driver mutations or potential therapeutic targets are not fully elucidated. Recent a few studies have shown that SCs have concurrently multiple mutations including RAS/RAF/MAPK and PI3K/Akt pathways via next-generation sequencing in western population. Because we recently demonstrated absence of KRAS mutations in Korean eyelid SCs, we extended our previous study to the analysis of NRAS, BRAF, PIK3CA, and CTNNB1 mutations, and the examination of related protein expressions in 15 eyelid SCs. Repeated molecular analysis by peptide nucleic acid-mediated PCR clamping method, PNA clamping-assisted fluorescence melting curve analysis, and direct sequencing revealed that all eyelid SCs had wild type alleles of NRAS, BRAF, and PIK3CA in hotspot exon locations. Only silent mutations in the CTNNB1 gene (p.Q61Q) were identified. Using immunohistochemistry and microsatellite instability analysis, they harbored all intact mismatch repair gene proteins with microsatellite stability. Membranous and cytoplasmic β-catenin staining was found in all tumors, whereas the one third of those tumors showed cyclin D1 overexpression, of which 40% and 80% showed p53 expression and p16 expression, respectively. The lack of KRAS, NRAS, BRAF, and PIK3CA mutation in our study may suggest that a subset of eyelid SCs is unlike that of eyelid SCs of western countries. The mismatch repair gene proteins and microsatellite instability analysis as a screening test for Muir-Torre syndrome may be limited in the Korean eyelid SCs.
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http://dx.doi.org/10.1016/j.prp.2017.02.015DOI Listing
June 2017

CD3 and CD20 Immunohistochemical Staining Patterns of Bone Marrow-Infiltrating Malignant Lymphoma Cells.

Ann Clin Lab Sci 2017 Mar;47(2):136-143

Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea

Objectives: It is known that CD3 and CD20 are homogenously expressed in T lineage and B lineage lymphoma, respectively; however, there are no standard guidelines to interpret immunohistochemistry findings. In this study, we investigated CD3 and CD20 immunohistochemical staining patterns of bone marrow (BM)-infiltrating lymphoma cells.

Methods: Among 297 patients diagnosed with malignant lymphoma, the BM biopsy slides of all 39 cases found to have BM infiltration (T lineage: 11; B lineage: 28) were reviewed. We specifically investigated the immunohistochemical staining patterns of CD3 and CD20.

Results: All 11 T lineage lymphoma cases showed homogenous immunohistochemical staining patterns. In the 28 B lineage lymphoma cases, 15 (53.6%) showed a homogenous pattern while 13 (46.4%) showed a heterogeneous pattern. Ten cases in the latter group showed additional evidence of BM infiltration by lymphoma cells in separate laboratory analyses or imaging studies. There were no differences in overall or progression-free survival rates in patients exhibiting homogeneous vs. heterogeneous staining patterns (=0.81 and P=0.59, respectively).

Conclusions: A considerable number of B lineage cases showed heterogeneous patterns with evidence of BM infiltration. Thus, heterogeneous immunohistochemical staining patterns (particularly in B lineage lymphomas) may signify malignant lymphoma cell infiltration into the BM.
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March 2017

Concurrent MET copy number gain and KRAS mutation is a poor prognostic factor in pancreatobiliary subtype ampullary cancers.

Pathol Res Pract 2017 Apr 11;213(4):381-388. Epub 2017 Jan 11.

Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Gyeonggi-do 431-070, Republic of Korea.

Hepatocyte growth factor (HGF) and MET are candidates of targeted therapies for cancer patients. Although MET and HGF are commonly expressed in biliary tract cancers, their expression and gene copy number status and their association with KRAS mutations have not been investigated in pancreatobiliary-type ampullary adenocarcinomas (A-ACs), one of the aggressive periampullary cancers. MET and HGF expressions and MET copy number status were examined by performing immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 62 surgically resected, paraffin-embedded tumors, respectively. High MET and HGF protein expressions were detected in 24 (38.7%) and 15 (24.2%) tumors. High MET expression was associated with KRAS mutation. However, there were no associations of high MET/HGF expression alone with other clinicopathological feature or survival. MET SISH positivity was detected in 19 tumors (30.6%), where 84.2% were due to high trisomy or polysomy and only 3 cases (15.8%) were MET gene amplification. The overall MET protein overexpression was well correlated with MET SISH positivity. The concurrent MET SISH positivity and KRAS mutation, not each alone, was an independent poor prognostic factor of disease-free survival only in pancreatobiliary subtype of A-ACs, but not in intestinal subtype. Concurrent MET SISH positivity and KRAS mutation may predict a high risk of recurrence in pancreatobiliary subtype of A-ACs, indicating those markers could be potent candidates for a new therapeutic target in this cancer type. MET IHC can be used as a reliable tool screening for MET copy number status in ampullary cancers.
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http://dx.doi.org/10.1016/j.prp.2017.01.004DOI Listing
April 2017

Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach.

World J Surg 2017 Jan;41(1):232-240

Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, Republic of Korea.

Background: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients.

Methods: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (≤3; 3-10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared.

Results: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05).

Conclusions: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma.
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http://dx.doi.org/10.1007/s00268-016-3687-7DOI Listing
January 2017

Extensive Lobular Carcinoma In Situ with Pagetoid Spread into Multiple Papillomas of the Breast.

Breast J 2016 Nov 4;22(6):693-695. Epub 2016 Aug 4.

Division of Breast and Endocrine Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

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http://dx.doi.org/10.1111/tbj.12660DOI Listing
November 2016

A case report of spindle cell myoepithelioma with extensive lipomatous metaplasia and thick collagen bundles in the submandibular gland.

Diagn Cytopathol 2016 Sep 16;44(9):764-9. Epub 2016 Jun 16.

Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University, College of Medicine, Seoul, Republic of Korea.

Spindle cell myoepithelioma with extensive lipomatous metaplasia and thick collagen bundles has not yet been described, and there are no published reports on its cytological appearance in fine-needle aspiration (FNA). A 49-year-old man presented with a painless mass in the right submandibular area that had been gradually enlarging for a period of 5 years. The cytologic smears showed fascicles of cohesive spindle cells as well as individual bland cells with bipolar naked nuclei in a fibrillary background. Brightly eosinophilic bundles were intermingled with spindle cells and fat-like vacuoles. The FNA results were suggestive of neurogenic tumor. Patient underwent submandibular gland resection. Grossly, the cut surface showed a well-encapsulated, yellowish-white, soft, elastic mass, measuring 2.8 × 1.9 × 1.5 cm. The tumor consisted of uniform bland spindle cells arranged in short fascicles admixed with adipocyte-like cells and transversing thick collagen bundles, which demonstrated immunoreactivity for myoepithelial markers and ultrastructural features characteristic of myoepithelial cells, suggesting the presence of lipomatous metaplasia. The FNA cytology of spindle cell myoepithelioma with extensive lipometaplasia mimicked that of neurogenic tumor or lipomatous mesenchymal tumor. This case represents the first description of submandibular gland myoepithelioma with lipometaplasia, which is characterized by the coexistence of spindle cells, collagen bundles, and fat-like vacuoles in a fibrillary background. Diagn. Cytopathol. 2016;44:764-769. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/dc.23513DOI Listing
September 2016

Low incidence of KRAS, BRAF, and PIK3CA mutations in adenocarcinomas of the ampulla of Vater and their prognostic value.

Hum Pathol 2016 Apr 30;50:90-100. Epub 2015 Nov 30.

Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea. Electronic address:

Ampullary adenocarcinomas (A-ACs) are rare malignancies with considerable importance because of their high curable resection rate and improved survival rate among periampullary cancers. The RAS-RAF-MAPK pathway is involved in the development of A-ACs and is a potential therapeutic target. However, molecular profiles of A-ACs and their prognostic impact are poorly understood. Peptide nucleic acid-mediated polymerase chain reaction clamping and Mutyper were used to detect KRAS, BRAF, and PIK3CA mutations in 62 paraffinized samples of A-ACs. Of 62 A-ACs, 30.6% had KRAS mutations, but no BRAF mutations and low frequency (1.6%) of PIK3CA mutation were detected. KRAS mutation was correlated with poor tumor differentiation and was a predictor of shorter recurrence-free survival period in overall A-ACs, whereas the prognosis according to the histologic subtypes was not affected by KRAS mutation. Lymph node metastasis was an independent prognostic factor of poor overall survival. Intestinal- and pancreatobiliary-type A-ACs had similar prognosis. Intestinal- and pancreatobiliary-type A-ACs had different prognostic factors; tumor differentiation and lymph node metastasis strongly predicted overall survival and recurrence-free survival in pancreatobiliary-type tumors, respectively, whereas no independent prognostic factors were demonstrated for intestinal-type tumors. Low incidence of KRAS mutations and their strong prognostic value in A-ACs may suggest the potential of survival benefit depending on the epidermal growth factor receptor-targeted therapy. Much lower frequencies of BRAF and PIK3CA mutations may suggest that they do not play a major role in the tumorigenesis of A-ACs. Different therapeutic protocols should be considered for treating pancreatobiliary- and intestinal-type A-ACs.
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http://dx.doi.org/10.1016/j.humpath.2015.11.009DOI Listing
April 2016

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis.

J Pathol Transl Med 2016 Mar 14;50(2):113-21. Epub 2015 Dec 14.

Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

Background: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs.

Methods: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically.

Results: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers.

Conclusions: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.
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http://dx.doi.org/10.4132/jptm.2015.10.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804146PMC
March 2016

Associations of the BRAF (V600E) mutation and p53 protein expression with clinicopathological features of papillary thyroid carcinomas patients.

Oncol Lett 2015 Sep 22;10(3):1882-1888. Epub 2015 Jun 22.

Department of Occupational and Environmental Medicine, Hallym University Sacred Heart Hospital, Anyang-si, Gyeonggi-do 431-796, Republic of Korea.

The BRAF (V600E) mutation is the most prevalent type of genetic alteration that has been identified in papillary thyroid carcinoma (PTC); in addition, previous immunohistochemical studies have revealed the overexpression of p53 protein in PTC. The aim of the present study was to investigate the prevalence of the BRAF (V600E) mutation and the expression of p53 in PTC, as well as to determine any associations between these two factors and the clinicopathological features of PTC. The study was performed on 66 PTC patients who underwent surgical tumor resection between January and December 2012. Polymerase chain reaction-based DNA amplification was used to analyze extracted DNA from the tumor specimens in order to determine the prevalence of the BRAF (V600E) mutation. In addition, immunohistochemical analysis was employed in order to evaluate the protein expression of p53 in sections of tumor tissue. Furthermore, statistical analysis was performed in order to determine any associations among the BRAF (V600E) mutation prevalence, p53 overexpression and the clinicopathological features of PTC patients, including age, gender, tumor size, multiplicity, lymph node metastasis and extrathyroidal extension. The results revealed that the BRAF (V600E) mutation was observed in 50 (75.8%) of the 66 PTC patients and overexpression of p53 was found in 52 (78.8%) of 66 cases. No significant correlations were observed between the BRAF (V600E) mutation or p53 protein overexpression and the clinicopathological features of patients. However, the BRAF (V600E) mutation demonstrated noteworthy, but non-significant, correlations with the overexpression of p53 (P=0.0854) and extrathyroidal extension (P=0.0661). In addition, a significant correlation was observed between lymph node metastasis and bilaterality (P=0.0280). In conclusion, the present study demonstrated that the BRAF (V600E) mutation and overexpression of p53 were not significantly correlated with clinicopathological features of PTC, although notable associations were identified between BRAF (V600E) mutation and overexpression of p53 as well as extrathyroidal extension. In addition, lymph node metastasis was significantly associated with bilaterality.
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http://dx.doi.org/10.3892/ol.2015.3401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533733PMC
September 2015

Incremental value of cell block preparations over conventional smears alone in the evaluation of EUS-FNA for pancreatic masses.

Hepatogastroenterology 2014 Oct;61(135):2117-22

Background/aims: The effectiveness of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established for a definite pathological diagnosis of pancreatic solid masses. We investigated the usefulness of cell block preparations in EUS-FNA, by evaluating the added value of cell block preparations over conventional smears alone.

Methodology: Between March 2011 and June 2013, 61 patients were retrospectively evaluated who underwent EUS-FNA for pancreatic solid masses. Diagnostic values for diagnosing pancreatic malignancy were compared for a combination of the conventional smear and cell block (CSCB) and the conventional smear alone (CS).

Results: The addition of the cell block technique increased the sensitivity of conventional smear for diagnosing the pancreatic malignancy from 79% (CS) to 90% (CSCB, p=0.0313) and the accuracy from 81% to 91% (p=0.0313). The specificity and positive predictive value were 100% in both methods. The negative predictive value was increased from 33% (CS) to 50% (CSCB), but this difference was not statistically significant (p=0.0833).

Conclusion: The addition of the cell block method after a conventional smear may increase the sensitivity and negative predictive value for diagnosing the pancreatic malignancy in patients with pancreatic masses who undergo EUS-FNA. Further study may be warranted to determine whether the cell block method can replace the conventional smear.
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October 2014

HIPK2 expression in progression of cutaneous epithelial neoplasm.

Int J Dermatol 2015 Mar;54(3):347-54

Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, Korea.

Background: Homeodomain-interacting protein kinase 2 (HIPK2) is responsible for a DNA damage response, centrally regulating p53. The aberrant HIPK2 expression is known to be involved in carcinogenesis in several malignancies. However, the correlation of HIPK2 expression along with progression of cutaneous epithelial neoplasm has not been investigated.

Methods: Using immunohistochemistry and real-time reverse transcription-polymerase chain reaction, we examined the correlation between HIPK2 and HIPK2-related protein expressions and the progression of some cutaneous epithelial neoplasms (i.e., actinic keratosis, Bowen's disease, keratoacanthoma, squamous cell carcinoma, and basal cell carcinoma).

Results: HIPK2 expression was distinct between preinvasive and invasive lesions: the expression decreased in keratoacanthoma (none of eight) and squamous cell carcinoma (five of 35) compared to actinic keratosis (12 of 19) and Bowen's disease (10 of 23) (P < 0.001). HIPK2 expression was also negatively correlated with aggressiveness of basal cell carcinoma; high-risk subtypes showed lower HIPK2 expression than did low-risk subtypes (P < 0.001). HIPK2 mRNA expression of each tumor group was significantly higher than that of normal skin. HIPK2 mRNA expression of each tumor group was not correlated with the relevant HIPK2 protein expression, which was consistent with previous studies.

Conclusions: HIPK2 expression tends to be decreased along tumor progression and may be involved with the invasive potential, suggesting a possible tumor suppressor role for HIPK2.
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http://dx.doi.org/10.1111/ijd.12664DOI Listing
March 2015

TCL1 expression predicts overall survival in patients with mantle cell lymphoma.

Eur J Haematol 2015 Dec 16;95(6):583-94. Epub 2015 Mar 16.

Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objectives: Mantle cell lymphoma (MCL) has a heterogeneous clinical course. Although most cases show a poor prognosis, a minority has an indolent course. It is difficult to identify indolent MCL cases prospectively. T-cell leukemia/lymphoma protein 1 (TCL1) is expressed by several B-cell lymphomas, including MCL. This study examined the expression of TCL1 and its prognostic relevance for MCL.

Methods: Clinical data for 162 patients with MCL were collected. Of these, 144 cases with available tissues for tissue microarray construction and immunostaining were included in the analysis. TCL1 staining was quantified using the Nuclear Quant application with Pannoramic™ Viewer v. 1.14. High TCL1 expression was defined as moderate to strong nuclear and/or cytoplasmic staining in 40% or more of the cells.

Results: High TCL1 expression was observed in 39 of 144 samples (27.1%). Patients with low TCL1 expression were more likely to present with blastoid/pleomorphic morphology (P = 0.010). Low TCL1 expression was associated with significantly shorter overall survival (OS, P = 0.006). Multivariate analysis identified low TCL1 expression (P = 0.003), high-risk MIPI (P = 0.027), and anemia (P = 0.018) as adverse prognostic factors.

Conclusions: Our study suggests that TCL1 expression profile may have a role in the prediction of overall outcome in patient with MCL and call for prospective studies.
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http://dx.doi.org/10.1111/ejh.12539DOI Listing
December 2015

The Clinical Utility of FDG PET-CT in Evaluation of Bone Marrow Involvement by Lymphoma.

Cancer Res Treat 2015 Jul 24;47(3):458-64. Epub 2014 Nov 24.

Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

Purpose: Bone marrow biopsy is a standard method for the evaluation of bone marrow infiltration by lymphoma; however, it is an invasive and painful procedure. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is a noninvasive imaging technique with the potential to detect bone marrow involvement by lymphoma.

Materials And Methods: We retrospectively reviewed medical records of lymphoma patients. All patients were examined by FDG PET-CT and iliac crest bone marrow biopsy for initial staging work-up.

Results: The study population comprised 94 patients (median age, 60 years; 56 males) with Hodgkin's lymphoma (n=8) or non-Hodgkin's lymphoma (n=86). Maximum standardized uptake values on the iliac crest of patients with lymphoma infiltrated bone marrow were significantly higher than those of patients with intact bone marrow (2.2±1.2 g/mL vs. 1.3±0.4 g/mL; p=0.001). The calculated values for FDG PET-CT during evaluation of bone marrow involvement were as follows: sensitivity 50%, specificity 96%, positive predictive value 80%, negative predictive value 85%, and positive likelihood ratio (LR+) 11.7. The value of LR+ was 16.0 in patients with aggressive subtypes of non-Hodgkin's lymphoma (NHL).

Conclusion: FDG PET-CT could not replace bone marrow biopsy due to the low sensitivity of FDG PET-CT for detection of bone marrow infiltration in lymphoma patients. Conversely, FDG PET-CT had high specificity and LR+; therefore, it could be a useful tool for image-guided biopsy for lymphoma staging, especially for aggressive subtypes of NHL. In addition, unilateral bone marrow biopsy could be substituted for bilateral bone marrow biopsy in lymphoma patients with increased FDG uptake on any iliac crest.
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http://dx.doi.org/10.4143/crt.2014.091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506116PMC
July 2015

Expression of Histone Deacetylases HDAC1, HDAC2, HDAC3, and HDAC6 in Invasive Ductal Carcinomas of the Breast.

J Breast Cancer 2014 Dec 26;17(4):323-31. Epub 2014 Dec 26.

Department of Occupation and Environmental Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

Purpose: DNA deacetylation by histone deacetylase (HDAC) is an important mechanism involved in the oncogenic tumorigenesis of breast cancer. Previous studies have reported an association of the estrogen receptor (ER) with HDACs and demonstrated the efficacy of HDAC inhibitors for the treatment of breast cancers via in vitro experiments. In this study, we examined the association of HDAC expression with clinicopathological parameters and disease-specific survival.

Methods: Immunohistochemical (IHC) analysis of HDAC1, HDAC2, HDAC3, and HDAC6 was performed using tissue microarrays in 300 invasive ductal carcinomas. IHC scoring was determined by multiplication of the intensity (0 to 3) and the proportion (0 to 4) of staining, and we classified tumors into low- and high-HDAC expression groups.

Results: High expression of HDAC1 was correlated with the molecular subtype (p=0.001) and human epidermal growth factor 2 (HER2) amplification (p=0.012). High expression of HDAC6 was correlated with a younger age (p<0.001), ER expression (p=0.025), progesterone receptor expression (p=0.034), molecular subtype (p=0.023), and HER2 amplification (p=0.011). High HDAC1 expression was correlated with luminal A tumors (p=0.001), while high HDAC6 expression was more common in luminal B tumors (p=0.023). Although the expression of HDACs did not exhibit prognostic significance in the entire cohort, high expression of HDAC1 and HDAC6 was associated with improved overall survival (OS) in patients with ER-positive tumors (p=0.017 and p=0.029, respectively), and high expression of HDAC2 was correlated with improved OS in ER-negative tumors (p=0.048) on univariate analysis. Furthermore, high HDAC6 expression was associated with improved disease-free survival (p=0.048) on multivariate analysis.

Conclusion: HDAC1 expression is significantly correlated with the molecular subtypes of tumors, with the highest expression being observed in luminal A tumors. HDAC6 is a significantly correlated with ER expression and the molecular subtype, thereby supporting the estrogen regulatory property of HDAC6. HDAC1 and HDAC6 expression are good prognostic factors for ER-positive tumors.
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http://dx.doi.org/10.4048/jbc.2014.17.4.323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278050PMC
December 2014

Simultaneous Occurrence of Ductal Carcinoma In Situ within Juvenile Fibroadenoma in Both Breasts: A Brief Case Report.

Korean J Pathol 2014 Apr 28;48(2):164-6. Epub 2014 Apr 28.

Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

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http://dx.doi.org/10.4132/KoreanJPathol.2014.48.2.164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026810PMC
April 2014

Characteristics of Cutaneous Lymphomas in Korea According to the New WHO-EORTC Classification: Report of a Nationwide Study.

Korean J Pathol 2014 Apr 28;48(2):126-32. Epub 2014 Apr 28.

Department of Pathology, Seoul National University, Seoul, Korea.

Background: Previously, cutaneous lymphomas were classified according to either the European Organization for the Research and Treatment of Cancer (EORTC) or the World Health Organization (WHO) classification paradigms. The aim of this study was to determine the relative frequency of Korean cutaneous lymphoma according to the new WHO-EORTC classification system.

Methods: A total of 517 patients were recruited during a recent 5 year-period (2006-2010) from 21 institutes and classified according to the WHO-EORTC criteria.

Results: The patients included 298 males and 219 females, and the mean age at diagnosis was 49 years. The lesions preferentially affected the trunk area (40.2%). The most frequent subtypes in order of decreasing prevalence were mycosis fungoides (22.2%), peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of which were secondary cutaneous involvement; other types of B-cell lymphoma accounted for less than 1% of cases.

Conclusions: In comparison with data from Western countries, this study revealed relatively lower rates of mycosis fungoides and B-cell lymphoma in Korean patients, as well as higher rates of subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma.
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http://dx.doi.org/10.4132/KoreanJPathol.2014.48.2.126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026803PMC
April 2014