Publications by authors named "Sanghui Park"

74 Publications

Diagnostic value of urine cytology in detecting histologic variants of urothelial carcinomas in the urinary bladder: Cytopathologic correlation of 72 cases.

Diagn Cytopathol 2021 Mar 16;49(3):367-373. Epub 2020 Dec 16.

Department of Pathology, Ewha Womans University College of Medicine, Seoul, South Korea.

Background: Precise identification of histologic variants in urothelial carcinoma (UC) is important because some histologic types have a poor prognosis and clinical management varies. Urine cytology is used for bladder cancer screening, but the cytomorphologic features of histologic variants have not been well described. In the current study, we evaluate the effectiveness of urine cytology in detecting histologic variants of UC in the urinary bladder.

Methods: Seventy-two urine cytology specimens from patients diagnosed with high-grade UCs by radical cystectomy were retrospectively reviewed and correlated with histopathologic findings of subsequent radical cystectomy specimens.

Results: Of 72 total cases, 24 (33%) cases showed six histologic variants in corresponding surgical specimens, including squamous differentiation (13 cases), plasmacytoid variant (3 cases), micropapillary variant (3 cases), sarcomatoid variant (3 cases), giant cell variant (1 case), and glandular differentiation (1 case). Histopathology and cytomorphology were well correlated in 13 cases (54%), with squamous differentiation in 11 of 13 cases (85%), micropapillary features in 1 out of 3 cases (33%), and spindle cell/sarcomatoid features in 1 of 3 cases (33%). Furthermore, mucosal involvement by histologic variants, not amount of histologic variant, was related to high concordance rates between cytology and histology diagnosis.

Conclusions: The morphologic features of some histologic variants of high-grade UCs, such as squamous differentiation, micropapillary variant, and sarcomatoid variant, are partially reflected on urine cytology. In addition, mucosal involvement by histologic variants was associated with a higher detection rate of histologic variants in urine cytology.
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http://dx.doi.org/10.1002/dc.24660DOI Listing
March 2021

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution's 20-year experience.

J Pathol Transl Med 2021 Mar 3;55(2):94-101. Epub 2020 Dec 3.

Department of Pathology, Ewha Womans University College of Medicine, Seoul, Korea.

Background: Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology.

Methods: We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding.

Results: Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis.

Conclusions: Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.
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http://dx.doi.org/10.4132/jptm.2020.10.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987521PMC
March 2021

Primary Female Urethral Carcinoma: Proposed Staging Modifications Based on Assessment of Female Urethral Histology and Analysis of a Large Series of Female Urethral Carcinomas.

Am J Surg Pathol 2020 12;44(12):1591-1601

Departments of Pathology.

Primary female urethral carcinoma is rare. Limited clinicopathologic information has hindered development of staging criteria in this disease. We analyzed 29 primary female urethral carcinoma resections from 3 academic medical centers to characterize histopathologic features, clinical outcomes, and applicability of current and a novel modified staging criteria. We complemented this analysis with review of fully embedded female autopsy urethras to detail anterior and posterior urethral wall histology. Primary female urethral carcinoma subtypes included urothelial carcinoma in situ (3/29, 10%), adenocarcinoma in situ (1/29; 3%), invasive urothelial carcinoma (13/29, 45%), clear cell carcinoma (5/29, 17%), adenocarcinoma not otherwise specified (4/29, 14%) and squamous cell carcinoma (3/29, 10%). Only 6/29 cases (21%) were originally assigned a stage at diagnosis. Using histologic landmarks specific to the female urethra, we modified existing eighth edition American Joint Committee on Cancer urethral staging to a histology-based female urethral carcinoma staging (UCS) system. UCS stages were defined as pTa/pTisUCS (noninvasive carcinoma), pT1UCS (subepithelial tissue invasion), pT2UCS (periurethral muscle invasion), pT3UCS (vaginal adventitia or surrounding fibrovascular tissue), and pT4UCS (anterior wall fibroadipose tissue or posterior vaginal wall). UCS staging was applicable to all cases and showed stepwise changes in disease recurrence with increasing stage and was statistically significant for disease-specific and overall survival in contrast to the American Joint Committee on Cancer staging system. This study of one of the largest cohort of primary female urethral carcinomas provides a modified histology-based staging system specific to female urethral anatomy that provides outcomes-related information, which may be further validated by larger multi-institutional studies.
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http://dx.doi.org/10.1097/PAS.0000000000001569DOI Listing
December 2020

Amplification of transglutaminase 2 enhances tumor-promoting inflammation in gastric cancers.

Exp Mol Med 2020 05 28;52(5):854-864. Epub 2020 May 28.

Department of Life Science, Ewha Womans University, Seoul, Korea.

Tumor-promoting inflammation is a hallmark of cancer and is highly associated with tumor progression, angiogenesis, and metastasis. Tumor-associated macrophages (TAMs) are major drivers of tumor-promoting inflammation, but due to the complexity of the tumor microenvironment, the detailed regulatory mechanisms are still under investigation. Here, we investigated a novel role for transglutaminase 2 (TGM2) in the development of tumor-promoting inflammation and recruitment of TAMs to gastric cancer (GC) tissues. When estimated by array comparative genomic hybridization and droplet digital PCR, the copy numbers of the TGM2 gene were amplified in 13.6% (14/103) of GC patients and positively associated with TGM2 expression. Gene set enrichment analysis of expression microarray data for GC samples with high or low TGM2 expression showed that increased TGM2 expression was associated with tumor-promoting inflammation in GC. In addition, the expression of TGM2 was correlated with the expression of markers for macrophages, neutrophils, blood vessels, and lymphatic vessels. Overexpression of TGM2 in GC cells augmented the IL-1β-induced secretion of macrophage-recruiting chemokines and NF-κB activation. TGM2 protein levels were associated with the expression levels of the macrophage marker CD163 in human GC tissue samples. Moreover, GC patients with high expression of TGM2 had a worse prognosis than those with low expression of TGM2. These results suggest TGM2 as a novel regulator of the tumor microenvironment of GC and provide a promising target for constraining tumor-promoting inflammation.
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http://dx.doi.org/10.1038/s12276-020-0444-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272405PMC
May 2020

Motion microscopy for label-free detection of circulating breast tumor cells.

Biosens Bioelectron 2020 Jun 1;158:112131. Epub 2020 Apr 1.

Department of Pharmacology, College of Medicine, Ewha Womans University, Seoul, Republic of Korea. Electronic address:

Circulating tumor cells (CTCs) are cancer cells that have been shed from a primary tumor and circulate in the bloodstream during progression of cancer. They may thus serve as circulating biomarkers that can predict, diagnose and guide therapy. Moreover, phenotypic and genotypic analysis of CTCs can facilitate prospective assessment of mutations and enable personalized treatment. A number of methodologies based on biological and physical differences between circulating tumor and non-tumor cells have been developed over the past few years. However, these methods did not have sufficient sensitivity or specificity. In this work, a remote analysis protocol was designed using motion microscopy that amplifies cellular micro motions in a captured video by re-rendering small motions to generate extreme magnified visuals to detect dynamic motions that are not otherwise visible by naked eye. Intriguingly, motion microscopy demonstrated fluctuations around breast tumor cells, which we referred to herein as cellular trail. Phenomena of cellular trail mostly emerged between 0.5 and 1.5 Hz on amplified video images. Interestingly, cellular trails were associated with cell surface proteins and flow rates rather than mitochondrial activity. Moreover, cellular trails were present only around circulating tumor cells from individuals with breast cancer under conditions of 20-30 μm/s and 0.5-1.5 Hz. Thus, motion microscopy based CTC detection method can offer a valuable supplementary diagnostic tool for assessment of drug efficacy and identifying physical characteristics of tumor cells for further research.
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http://dx.doi.org/10.1016/j.bios.2020.112131DOI Listing
June 2020

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate.

J Pathol Transl Med 2020 Mar 10;54(2):146-153. Epub 2020 Feb 10.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital and Weill Medical College of Cornell University, Houston, TX, USA.

Background: Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.

Methods: Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.

Results: In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.

Conclusions: Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.
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http://dx.doi.org/10.4132/jptm.2019.11.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093285PMC
March 2020

Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations.

Ann Diagn Pathol 2020 Feb 22;44:151433. Epub 2019 Nov 22.

Department of Pathology and Genomic Medicine, The Methodist Hospital and Weill Medical College of Cornell University, Houston, TX 77030, USA. Electronic address:

Background: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking.

Methods: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed.

Results: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2.

Conclusions: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.
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http://dx.doi.org/10.1016/j.anndiagpath.2019.151433DOI Listing
February 2020

Degranulated Eosinophils Contain More Fine Nerve Fibers in the Duodenal Mucosa of Patients With Functional Dyspepsia.

J Neurogastroenterol Motil 2019 Apr;25(2):212-221

Department of Pathology, College of Medicine, Ewha Womans University, Seoul, Korea.

Background/aims: Functional dyspepsia (FD) is characterized as chronic recurrent upper gastrointestinal symptoms in the absence of any organic disorder. We hypothesized that duodenal low-grade inflammation activates superficial afferent nerve sprouting, thereby contributing to hypersensitivity in patients with FD.

Methods: A prospective case-control study was conducted in a tertiary referral center. FD was defined using the Rome III criteria. Standardized endoscopic biopsies were performed in the stomach and duodenum. Hematoxylin and eosin staining and immunohistochemical staining for major basic proteins were performed to detect granulated eosinophil-derived granules, and S-100 staining was performed to detect fine nerve fibers.

Results: A total of 51 patients with FD (82% female; mean age 35.8 ± 13.4 years) and 35 controls were enrolled. Activated eosinophil counts in the duodenum were significantly higher in patients with FD than in controls (41.4% vs 17.1%, = 0.005). Microscopic duodenitis was more frequently detected in patients with FD than in controls. Fine nerve fibers were more abundant in patients with FD than in controls (45.1% vs 11.4%, = 0.029). The abundance of fine nerve fibers highly correlated with the degree of activated eosinophils.

Conclusion: Duodenal low-grade inflammation, such as mucosal eosinophilic accumulation with degranulation, promoted mucosal enteric nerve fiber density and sprouting in patients with FD.
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http://dx.doi.org/10.5056/jnm18176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474707PMC
April 2019

MiR-34a and miR-34b/c have distinct effects on the suppression of lung adenocarcinomas.

Exp Mol Med 2019 01 17;51(1):1-10. Epub 2019 Jan 17.

Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, 07985, Korea.

Three miR-34 family members (miR-34a, miR-34b, and miR-34c) are clustered on two different chromosomal loci, Mir34a and Mir34b/c. These miRNAs have identical seed sequences, which are predicted to target the same set of genes. However, miR-34a and miR-34c have different sets of negatively correlated genes in lung adenocarcinoma data from The Cancer Genome Atlas. Therefore, we hypothesized that the individual miR-34 family members, which are tumor suppressive miRNAs, would have varying effects on lung tumorigenesis. To show this, we overexpressed each miR-34 cluster in murine lung cancer cells. MiR-34b/c enhanced cancer cell attachment and suppressed cell growth and invasion compared with miR-34a. In a syngeneic mouse model, both miR-34a and miR-34b/c blocked lung metastasis. However, miR-34b/c suppressed tumor growth more than miR-34a. MiR-34b/c also decreased the expression of mesenchymal markers (Cdh2 and Fn1) and increased the expression of epithelial markers (Cldn3, Dsp, and miR-200) to a greater degree than miR-34a. These results imply that miR-34b and miR-34c inhibit epithelial-to-mesenchymal transition. Furthermore, knockout of all three miR-34 members promoted mutant Kras-driven lung tumor progression in mice. Similarly, lung adenocarcinoma patients with higher miR-34a/b/c levels had better survival rates than did those with lower levels. In summary, we suggest that miR-34b and miR-34c are more effective tumor suppressors than miR-34a.
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http://dx.doi.org/10.1038/s12276-018-0203-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353903PMC
January 2019

Non-urothelial carcinomas of the bladder.

Histopathology 2019 Jan;74(1):97-111

Department of Pathology, University of California at San Diego, La Jolla, CA, USA.

Non-urothelial carcinomas involving the bladder are uncommon and often diagnostically challenging. These carcinomas may show squamous, adenocarcinomatous or neuroendocrine features, with immunohistochemical stains aiding the diagnosis in only a subset of cases. The clinical history in non-urothelial bladder carcinomas is important, given that the differential diagnosis often includes secondary involvement of the bladder by direct extension or metastasis from carcinomas at other sites. This paper will review non-urothelial carcinomas in each of these three morphological categories, emphasising recent changes in diagnostic grouping and challenges in the histopathological diagnosis. Review of bladder cancers with squamous morphology will include discussion of conventional squamous cell carcinoma and verrucous carcinoma and their distinction from urothelial carcinoma with extensive squamous differentiation. Bladder carcinomas with adenocarcinomatous change will include primary bladder adenocarcinoma, urachal adenocarcinoma and tumours of Müllerian type. Finally, neuroendocrine neoplasms of the bladder, including well-differentiated neuroendocrine tumour and neuroendocrine carcinomas, will be discussed. Associated surface findings, risk factors and prognostic features will be described.
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http://dx.doi.org/10.1111/his.13719DOI Listing
January 2019

Urinary Exosomal and cell-free DNA Detects Somatic Mutation and Copy Number Alteration in Urothelial Carcinoma of Bladder.

Sci Rep 2018 10 2;8(1):14707. Epub 2018 Oct 2.

Department of Urology, Ewha Womans University College of Medicine, Seoul, Korea.

Urothelial bladder carcinoma (UBC) is characterized by a large number of genetic alterations. DNA from urine is a promising source for liquid biopsy in urological malignancies. We aimed to assess the availability of cell-free DNA (cfDNA) and exosomal DNA (exoDNA) in urine as a source for liquid biopsy in UBC. We included 9 patients who underwent surgery for UBC and performed genomic profiling of tumor samples and matched urinary cfDNA and exoDNA. For mutation analysis, deep sequencing was performed for 9 gene targets and shallow whole genome sequencing (sWGS) was used for the detection of copy number variation (CNV). We analyzed whether genetic alteration in tumor samples was reflected in urinary cfDNA or exoDNA. To measure the similarity between copy number profiles of tumor tissue and urinary DNA, the Pearson's correlation coefficient was calculated. We found 17 somatic mutations in 6 patients. Of the 17 somatic mutations, 14 and 12 were identified by analysis of cfDNA and exoDNA with AFs of 56.2% and 65.6%, respectively. In CNV analysis using sWGS, although the mean depth was 0.6X, we found amplification of MDM2, ERBB2, CCND1 and CCNE1, and deletion of CDKN2A, PTEN and RB1, all known to be frequently altered in UBC. CNV plots of cfDNA and exoDNA showed a similar pattern with those from the tumor samples. Pearson's correlation coefficients of tumor vs. cfDNA (0.481) and tumor vs. exoDNA (0.412) were higher than that of tumor vs. normal (0.086). We successfully identified somatic mutations and CNV in UBC using urinary cfDNA and exoDNA. Urinary exoDNA could be another source for liquid biopsy. Also, CNV analysis using sWGS is an alternative strategy for liquid biopsy, providing data from the whole genome at a low cost.
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http://dx.doi.org/10.1038/s41598-018-32900-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168539PMC
October 2018

Feasibility of Classification of Triple Negative Breast Cancer by Immunohistochemical Surrogate Markers.

Clin Breast Cancer 2018 10 23;18(5):e1123-e1132. Epub 2018 Mar 23.

Department of Pathology, Ewha Womans University School of Medicine, Yangcheongu, Seoul, Korea. Electronic address:

Introduction: Recently, Burstein et al identified 4 stable molecular subtypes of triple negative breast cancer (TNBC) by mRNA profiling: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immune-activated (BLIA), and basal-like immune-suppressive (BLIS) types. The purpose of this study was to assess the feasibility of immunohistochemistry (IHC) surrogate panel in classifying the TNBC molecular subtypes using a large cohort of TNBC retrieved from a single institution.

Materials And Methods: IHC for androgen receptor [AR], claudin-3, E-cadherin, cytokeratin 5/6 [CK5/6], epidermal growth factor receptor [EGFR], indoleamine 2,3-dioxygenase 1 [IDO1], and Forkhead box C1 [FOXC1] were performed using the tissue microarray constructed from 200 TNBC samples.

Results: The 200 TNBCs were classified as LAR (AR, n = 22; 11.0%), MES (claudin 3 and/or E-cadherin, n = 23; 11.5%), basal-like (CK5/6 and/or EGFR, n = 85; 42.5%), mixed (n = 60; 30%), and unclassifiable type (n = 10; 5%). LAR type was associated with older patient age, apocrine histologic features, low density of stromal tumor-infiltrating lymphocytes (TIL), and low Ki-67 labeling index. MES type was associated with tumor cell discohesiveness and metaplastic features. Basal-like type was associated with younger patient age, high histologic grade, high stromal TIL density, and high Ki-67 labeling index. Basal-like TNBCs were further classified as BLIA (IDO1 and FOXC1, n = 27) or BLIS type (IDO1 and FOXC1, n = 11). BLIS type was associated with large tumor size and low stromal TIL density, which had the worst prognostic outcome among 4 subtypes.

Conclusion: The IHC surrogate panel may define TNBC subtypes with distinct clinicopathologic characteristics and prognostic significance.
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http://dx.doi.org/10.1016/j.clbc.2018.03.012DOI Listing
October 2018

Antibiotics-Associated Hemorrhagic Colitis Caused by : Two Case Reports.

Pediatr Gastroenterol Hepatol Nutr 2018 Apr 13;21(2):141-146. Epub 2018 Apr 13.

Department of Pediatrics, Ewha Womans University College of Medicine, Seoul, Korea.

Nowadays, is described as a causative organism for antibiotic-associated hemorrhagic colitis (AAHC). Here we report two cases of pediatric AAHC, from which was cultured after starting amoxicillin-clavulanate or amoxicillin treatment. The patients developed severe abdominal pain and a large amount of bloody diarrhea. was obtained in intestinal fluid culture of a boy through the colonoscopy. On the other hand, colonic tissue culture and intestinal fluid culture were negative of the other patient. was detected in stool culture when he was admitted. These cases showed characteristic endoscopic findings of segmental hemorrhagic colitis, and both boys recovered spontaneously within 2-3 days after they stopped taking the antibiotics. Therefore, in children who develop relatively large amount of bloody diarrhea after antibiotic treatment, we should consider AAHC caused by .
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http://dx.doi.org/10.5223/pghn.2018.21.2.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915692PMC
April 2018

Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments.

Blood 2018 04 23;131(17):1931-1941. Epub 2018 Feb 23.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (EBV-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV-DLBLs are largely unknown because of the limited availability of human samples and lack of experimental animal models. We observed the development of 25 human EBV-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV-DLBLs revealed enrichment of mutations in Rho pathway genes, including , and Rho pathway transcriptomic activation. Targeting the Rho pathway using a Rho-associated protein kinase (ROCK) inhibitor, fasudil, markedly decreased tumor growth in EBV-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.
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http://dx.doi.org/10.1182/blood-2017-07-797209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921963PMC
April 2018

Value of imaging study in predicting pelvic lymph node metastases of uterine cervical cancer.

Radiat Oncol J 2017 Dec 15;35(4):340-348. Epub 2017 Dec 15.

Department of Pathology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.

Purpose: To evaluate the diagnostic accuracy of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) in predicting pelvic lymph node (LN) metastases in patients with cervical cancer.

Materials And Methods: From January 2009 to March 2015, 114 patients with FIGO stage IA1-IIB uterine cervical cancer who underwent hysterectomy with pelvic lymphadenectomy and took CT, MRI, and PET/CT before surgery were enrolled in this study. The criteria for LN metastases were a LN diameter ≥1.0 cm and/or the presence of central necrosis on CT, a LN diameter ≥1.0 cm on MRI, and a focally increased FDG uptake on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for pelvic LN metastases were estimated.

Results: The sensitivity, specificity, PPV, NPV, and accuracy for detection of pelvic LN metastases were 51.4%, 85.9%, 41.3%, 90.1%, and 80.3% for CT; 24.3%, 96.3%, 56.3%, 86.8%, and 84.6% for MRI; and 48.6%, 89.5%, 47.4%, 90.0%, and 82.9% for PET/CT, respectively. The sensitivity of PET/CT and CT was higher than that of MRI (p=0.004 and p= 0.013, respectively). The specificity of MRI was higher than those of PET/CT and CT (p=0.002 and p=0.001, respectively). The difference of specificity between PET/CT and CT was not statistically significant (p=0.167).

Conclusion: These results indicate that preoperative CT, MRI, and PET/CT showed low to moderate sensitivity and PPV, and moderate to high specificity, NPV, and accuracy. More efforts are necessary to improve sensitivity of imaging modalities in order to predict pelvic LN metastases.
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http://dx.doi.org/10.3857/roj.2017.00206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769886PMC
December 2017

Pitfalls of Frozen Section Diagnosis for Paraganglioma: A Clinicopathologic Analysis and Review of the Literature.

Int J Surg Pathol 2018 May 23;26(3):213-220. Epub 2017 Nov 23.

3 Department of Pathololgy, Sungkyunkwan University, Seoul, Republic of Korea.

Few paraganglioma (PG) cases include frozen section diagnoses, and therefore, the accuracy of frozen section diagnosis for PG remains unknown. To better understand the histologic characteristics and pitfalls of frozen section findings for PG, 15 PG cases with frozen section diagnoses were selected from 12 articles through PubMed (1984-2015). In addition, we included 3 cases of PG for which intraoperative consultations were requested during a 5-year period (2012-2016) in 2 hospitals. Seven PGs were from the thyroid; 2 from the pancreas; 4 from the mediastinum, retroperitoneum, or mesentery; 1 from the middle ear; and 4 from the urinary bladder (UB). Out of 18 PGs, correct diagnoses were rendered in only 2 cases, and no thyroid or UB PGs were correctly diagnosed on intraoperative consultation. Thyroid PGs were frequently misdiagnosed as medullary thyroid carcinomas (4/7, 57%) and UB PGs were frequently misdiagnosed as malignancies.
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http://dx.doi.org/10.1177/1066896917742199DOI Listing
May 2018

Evaluation of Ki-67 Index in Core Needle Biopsies and Matched Breast Cancer Surgical Specimens.

Arch Pathol Lab Med 2018 Mar 16;142(3):364-368. Epub 2017 Nov 16.

From the Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea (Dr Ahn); and the Department of Pathology, Ewha Womans University Medical Center, Seoul, Korea (Drs Lee, Cho, Park, and Sung).

Context: - The Ki-67 index is strongly prognostic and is used as a surrogate marker to distinguish luminal A from luminal B breast cancer types.

Objective: - To investigate differences in Ki-67 index between core needle biopsy samples and matched surgical samples in breast cancer.

Design: - We included patients with invasive breast cancer who did not receive neoadjuvant therapy. A total of 89 pairs of core needle biopsies and surgical specimens were collected, and the Ki-67 index was assessed in hot spot areas using an image analyzer. We applied a 14% Ki-67 index to define low versus high groups.

Results: - The Ki-67 index was significantly higher in core needle biopsies than in surgical specimens ( P < .001), with a median absolute difference of 3.5%. When we applied 14% as a cutoff, 16 of 89 cases (18%) showed discrepancy. Thirteen cases showed a high Ki-67 index in core needle biopsies but a low Ki-67 index in surgical samples. There were 10 cases (11.2%) that showed discordant luminal A/B types between core needle biopsy and the matched surgical specimen. The reasons for the discordance were poor staining of MIB1 accompanied by fixation issues and intratumoral heterogeneity of the Ki-67 index.

Conclusions: - A significant difference in the Ki-67 index between core biopsy and surgical specimens was observed. Our findings indicate that it may be better to perform the Ki-67 assay on the core needle biopsy and the surgical specimen than on only one sample.
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http://dx.doi.org/10.5858/arpa.2017-0014-OADOI Listing
March 2018

Identification of distinctive clinical significance in hospitalized patients with endoscopic duodenal mucosal lesions.

Korean J Intern Med 2017 Sep 21;32(5):827-835. Epub 2017 Aug 21.

Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.

Background/aims: Duodenitis is not infrequent finding in patient undergoing endoscopy. However, hospitalized patients have a higher incidence of secondary duodenal mucosal lesions that might be related with inflammatory bowel disease (IBD), cytomegalovirus (CMV) infection, tuberculosis, immunologic disorders, or other rare infections. We aimed to identify clinicopathologic features of duodenal mucosal lesions in hospitalized patients.

Methods: All hospitalized patients having duodenal mucosal lesions were identified by endoscopic registration data and pathologic data query from 2011 to 2014. The diagnostic index was designed to be sensitive; however, a detailed review of medical record and endoscopic findings was undertaken to improve specificity. Secondary duodenal lesion was defined as having specific reason to explain the duodenal lesion.

Results: Among 6,334 hospitalized patients have undergone upper endoscopy, endoscopic duodenal mucosal lesions was detected in 475 patients. Secondary duodenal lesions was 21 patients (4.4%) and the most frequent secondary cause was IBD (n = 7). The mean age of secondary group was significantly lower than that in primary group (42.3 ± 18.9 years vs. 58.5 ± 16.8 years, = 0.00), and nonsteroidal anti-inflammatory drugs were less frequently used in secondary group, but there was no differences of gender or presence of . The involvement of distal part of duodenum including postbulbitis or panduodenitis was more frequently detected in secondary group than in primary group. By multivariate regression analysis, younger age of 29 years and the disease extent were significant predictors for the secondary mucosal lesions.

Conclusions: Secondary duodenal mucosal lesions with different pathophysiology, such as IBD or CMV infection, are rare. Disease extent and age seems the most distinctive feature of secondary duodenal mucosal lesions.
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http://dx.doi.org/10.3904/kjim.2015.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583440PMC
September 2017

Level of mitoses in non-muscle invasive papillary urothelial carcinomas (pTa and pT1) at initial bladder biopsy is a simple and powerful predictor of clinical outcome: a multi-center study in South Korea.

Diagn Pathol 2017 Jul 24;12(1):54. Epub 2017 Jul 24.

Department of Pathology, Inje University Sanggye Paik Hospital, 1342, Dongilro, Nowon-gu, Seoul, South Korea.

Background: Histologic grade is the most important predictor of the clinical outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa), but its ambiguous criteria diminish its power to predict recurrence/progression for individual patients. We attempted to find an objective and reproducible histologic predictor of NMIPUCa that correlates well with the clinical outcome.

Methods: A total of 296 PUCas were collected from the Departments of Surgical Pathology of 11 institutions in South Korea. The clinical outcome was grouped into no event (NE), recurrence (R), and progression (P) categories. All 25 histological parameters were numerically redefined. The clinical pathology of each case was reviewed individually by 11 pathologists from 11 institutions based on the 2004 WHO criteria and afterwards blindly evaluated by two participants, based on our proposed parameters. Univariate and multivariate logistic regression analyses were performed using the R software package.

Results: The level of mitoses was the most reliable parameter for predicting the clinical outcome. We propose a four-tiered grading system based on mitotic count (> 10/10 high-power fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20), presence of divergent histology, and capillary proliferation (> 20 capillary lumina per papillary core).

Conclusions: The level of mitoses at the initial bladder biopsy and transurethral resection (TUR) specimen appeared to be an independent predictor of the Ta PUCa outcome. Other parameters include the number of mitoses, nuclear pleomorphism, divergent histology, and capillary proliferation within the fibrovascular core. These findings may improve selection of patients for a therapeutic strategy as compared to previous grading systems.
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http://dx.doi.org/10.1186/s13000-017-0639-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525253PMC
July 2017

Effects of anatomical characteristics as factors in abdominal aortic aneurysm rupture: CT aortography analysis.

Medicine (Baltimore) 2017 Jun;96(25):e7236

Department of Radiology and Medical Research Institute, Ewha Womans University College of Medicine Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul Department of Radiology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Kyeonggi-do Department of Pathology, Ewha Womans University College of Medicine, Seoul, Republic of Korea.

The aim of this study was to analyze the anatomical characteristics of patients with ruptured abdominal aortic aneurysms (AAAs) using computed tomography (CT) aortography in order to determine the risk factors for rupture.We retrospectively reviewed the CT aortography findings and medical records of patients with ruptured AAAs who underwent CT aortography between February 2002 and December 2014. Age, sex, blood pressure at the time of rupture, treatment methods used for the ruptured AAAs, and treatment outcomes were analyzed. Statistical analyses were performed to determine the association between the maximum aneurysm diameter, which is considered the standard predictor of aneurysm rupture, and anatomical characteristics such as proximal neck diameter, angle between the suprarenal aorta and the aneurysm neck (α angle), angle between the aneurysm neck and aneurysm sac (β angle), and angles between the abdominal aorta and both iliac arteries.Data were reviewed for a total of 36 patients. The mean maximum diameter of AAAs was 76.84 ± 21.08 mm. Multivariate analysis adjusted for age and sex indicated statistical correlations between the α and β angles and maximum aneurysm diameter and between the β angle and iliac artery involvement.Our results suggest that the tortuosity of the aorta tends to be associated with the diameter of AAAs and iliac artery involvement. Investigation of the anatomical characteristics of individual patients using CT aortography is expected to aid in predicting the risk of AAA rupture.
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http://dx.doi.org/10.1097/MD.0000000000007236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484229PMC
June 2017

Collagenoma in a Patient With Down Syndrome: A Case Report and Review of the Literature.

Am J Dermatopathol 2018 May;40(5):355-357

Departments of Radiology, and.

A 26-year-old woman with Down syndrome presented with a 4-cm-sized palpable mass in the sacrococcygeal region. Histologic evaluation of the specimen revealed densely packed collagen fibers in the dermis, which is consistent with a collagenoma. Masson trichrome staining showed dense fibrosis, and elastic Van Gieson staining revealed a significant decrease in elastic tissue. The clinicopathologic characteristics of this patient and 4 previously reported cases are discussed in detail.
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http://dx.doi.org/10.1097/DAD.0000000000000873DOI Listing
May 2018

Effect of a pH-Balanced Vaginal Gel on Dyspareunia and Sexual Function in Breast Cancer Survivors Who Were Premenopausal at Diagnosis: A Randomized Controlled Trial.

Obstet Gynecol 2017 05;129(5):870-876

Departments of Obstetrics and Gynecology and Pathology, Ewha Womans University School of Medicine, and the Department of Obstetrics and Gynecology, College of Medicine, and the Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea.

Objective: To assess whether a pH-balanced vaginal gel containing lactic acid is more effective than a placebo (lactate-free gel) in improving dyspareunia and sexual function among breast cancer survivors who were premenopausal at diagnosis and had dyspareunia after adjuvant chemotherapy.

Methods: In a single-center, double-blind, randomized trial, a pH-balanced gel or placebo was administered three times per week at bedtime as well as during sexual intercourse for 8 weeks. The primary outcome was the improvement of dyspareunia measured by pain score of the Female Sexual Function Index after the treatment. Secondary outcomes included the total and individual domains of Female Sexual Function Index score, sexual dysfunction (a total Female Sexual Function Index score less than 25.0), vaginal pH, vaginal maturation index, and adverse events related to the intervention. A sample size of 47 per group was planned to achieve 80% power to detect a 19% difference in the primary outcome.

Results: From October 2009 and March 2013, 167 women were screened and 136 were randomized: 69 to a pH-balanced gel and 67 to placebo. Baseline characteristics were similar in both groups. Although there was no difference between the two groups, both experienced a significant improvement of dyspareunia. The increase in median pain score from baseline was 1.2 in both groups (median [interquartile range] from 2.8 [2.0-4.0] to 4.0 [2.8-4.8] in the pH-balanced group and from 3.2 [2.0-4.0] to 4.4 [3.2-4.8] in the placebo group; all P<.01). Overall Female Sexual Function Index score and the frequency of sexual dysfunction also did not differ between the two groups although there was a significant improvement. On the other hand, vaginal pH and vaginal maturation index were slightly but significantly improved only in the pH-balanced group. There were no severe adverse events in either group.

Conclusion: The pH-balanced vaginal gel is not superior to the placebo in improving dyspareunia and overall sexual function.

Clinical Trial Registration: ClinicalTrials.gov, https://www.clinicaltrials.gov, NCT00981305.
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http://dx.doi.org/10.1097/AOG.0000000000001988DOI Listing
May 2017

Strong Correlation of Indoleamine 2,3-Dioxygenase 1 Expression with Basal-Like Phenotype and Increased Lymphocytic Infiltration in Triple-Negative Breast Cancer.

J Cancer 2017 1;8(1):124-130. Epub 2017 Jan 1.

Department of Pathology, Ewha Womans University School of Medicine, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Korea.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme involved in tumor immune escape. Blockade of the IDO1 pathway is an emerging modality of cancer immunotherapy. Triple-negative breast cancer (TNBC) lacks established therapeutic targets and may be a good candidate for this novel immunotherapeutic agent. The purpose of this study was to evaluate the clinicopathologic characteristics of the IDO1-expressing TNBC subset. A tissue microarray was constructed from 200 patients with TNBC. Immunohistochemistry (IHC) for IDO1 and TNBC molecular subtype-surrogate markers (AR, GCDFP-15, claudin-3, E-cadherin, CK5/6, and EGFR) was performed using this tissue microarray. Real-time polymerase chain reaction was performed to confirm the IDO1 mRNA expression level in 16 fresh-frozen TNBC samples. Two hundred TNBCs were classified into four subtypes based on surrogate IHC results: 22 luminal androgen receptor type (11.0%), 23 claudin-low type (11.4%), 103 basal-like type (51.5%), and 52 mixed type (26.0%). IDO1 positivity (defined as expression of >10% tumor cells) was observed in 37% of all TNBCs. IDO1 IHC expression was well correlated with mRNA expression. IDO1 positivity was significantly associated with smaller tumor size, dense stromal lymphocytic infiltration, and basal-like phenotype; however, it did not affect the patients' prognosis. IDO1 expression in basal-like TNBCs is considered an immune inhibitory signal that counterbalances active immunity and may reflect the high mutational load of these tumors. Our results suggest which patients with TNBC would be more efficaciously treated with IDO1 blockade.
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http://dx.doi.org/10.7150/jca.17437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264048PMC
January 2017

Urine cytology findings of primary paraganglioma of the urinary bladder: Case report.

Diagn Cytopathol 2017 Apr 22;45(4):350-353. Epub 2017 Jan 22.

Department of Urology, Ewha Womans University School of Medicine, Seoul, Korea.

Paraganglioma (PG) of the urinary bladder was detected in a 64-year-old male who was admitted to the hospital with gross hematuria. In voided urine, atypical cells were scattered as nests and single cells on low-power view. On higher-power view, tumor nests were composed of epithelioid cells with fine chromatin and moderate cytoplasm admixed with occasional spindle sustentacular cells. Single cells were discohesive and large with moderate cytoplasm and inconspicuous nucleoli. Subsequent cystoscopy revealed a solid oval mass. Histologically, tumor from the resected bladder showed infiltrating nested tumor cells with abundant cytoplasm. Immunohistochemically, the tumor cells were positive for synaptophysin, chromogranin, and CD56. The patient underwent partial cystectomy and was discharged without complications. Diagn. Cytopathol. 2017;45:350-353. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/dc.23667DOI Listing
April 2017

Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study.

Arch Pathol Lab Med 2017 May 7;141(5):671-677. Epub 2016 Nov 7.

From the Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea (Drs S. Park, S.H. Sung, and M.S. Cho); the Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea (Drs Kang and G.Y. Kwon); the Department of Pathology, Ajou University School of Medicine, Suwon, Korea (Dr J.E. Kwon); the Department of Pathology, Yonsei University College of Medicine, Seoul, Korea (Dr S.K. Kim and N.H. Cho); the Department of Pathology, Inje University Haeundae Paik Hospital, Pusan, Korea (Dr J.Y. Kim); the Department of Pathology, Korea University School of Medicine, Seoul, Korea (Drs C.H. Kim and Chae); the Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea (Dr H.J. Kim); the Department of Pathology and Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea (Dr Moon); the Department of Pathology, College of Medicine, Hanyang University Guri Hospital, Guri, Korea (Drs Pyo and Oh); the Department of Pathology, Pusan National University Hospital College of Medicine, Pusan, Korea (Dr W.Y. Park); the Department of Hospital Pathology, Incheon St Mary's Hospital, College of Medicine, Catholic University of Korea, Incheon, Korea (Dr E.S. Park); the Department of Pathology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea (Dr J.Y. Sung); the Department of Pathology, Konkuk University School of Medicine, Seoul, Korea (Dr S.E. Lee); the Department of Pathology, Dankook University College of Medicine, Cheonan, Korea (Dr W. Lee); the Department of Pathology, Dongguk University College of Medicine, Gyeonju, Korea (Dr J.I. Lee); the Department of Pathology, Inje University Busan Paik Hospital, Pusan, Korea (Dr Jung); the Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (Drs Y.M. Cho and Huh); the Department of Pathology, Gachon University Gil Medical Center, Incheon, Korea (Dr H.Y. Cho); the Department of Pathology, Konyang University School of Medicine, Daejeon, Korea (Dr Cha); the Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea (Dr Choe); the Department of Hospital Pathology, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea (Dr Choi); and the Department of Pathology and Genomic Medicine, The Methodist Hospital and Weill Medical College of Cornell University, Houston, Texas (Dr Ro).

Context: - Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied.

Objective: - To define the clinicopathologic and molecular characteristics of PBPGs.

Design: - A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed.

Results: - The clinicopathologic features were analyzed for 52 cases (M:F = 27:25), with a mean age of 56 years (range, 22-79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1-161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P < .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only.

Conclusions: - Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma.
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http://dx.doi.org/10.5858/arpa.2016-0403-OADOI Listing
May 2017

Increased plasmacytic differentiation in gastric mucosa-associated lymphoid tissue lymphomas: Helicobacter pylori eradication response and IgG4+ plasma cell association.

Hum Pathol 2017 01 30;59:113-119. Epub 2016 Sep 30.

Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351 Republic of Korea.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare extranodal marginal zone B-cell lymphoma that is often associated with plasmacytic differentiation. However, the clinicopathological characteristics of gastric MALT lymphoma with increased plasmacytic differentiation have not yet been studied. To assess the clinicopathological implications of gastric MALT lymphoma with increased plasmacytic differentiation, 36 cases with increased plasmacytic differentiation and a control group of 16 cases with minimal plasmacytic differentiation were retrospectively collected from 65 primary gastric MALT lymphomas (2010-2012). The hematoxylin and eosin slides were reviewed, and IgG, IgG4, and κ and λ immunohistochemical staining was performed. Clinicopathological differences between the 2 groups were compared using the χ test and odds ratios. Logistic regression analyses were used to evaluate resistance to Helicobacter pylori eradication therapy. Increased plasmacytic differentiation is significantly correlated with the H pylori eradication response (94.4% versus 66.7%, P=.018), lower frequency of relapse (5.6% versus 35.7%, P=.014), the presence of more than one IgG4+ cell per high-power field (27.8% versus 0%, P=.022), and light-chain restriction (33.3% versus 6.2%, P=.044). Univariable logistic regression indicated that negative H pylori status (P=.016) and minimal plasmacytic differentiation (P=.019) were statistically significant predictive factors for resistance to H pylori eradication. Multivariable logistic regression analyses identified no statistically significant predictive factors. However, H pylori negativity and minimal plasmacytic differentiation showed a statistical trend toward significance (P=.078 and P=.09). Gastric MALT lymphomas with increased plasmacytic differentiation have different clinicopathological characteristics, and plasmacytic differentiation is associated with H pylori eradication response.
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http://dx.doi.org/10.1016/j.humpath.2016.09.013DOI Listing
January 2017

Target sequencing and CRISPR/Cas editing reveal simultaneous loss of UTX and UTY in urothelial bladder cancer.

Oncotarget 2016 Sep;7(39):63252-63260

Department of Urology, Ewha Womans University School of Medicine, Seoul, Korea.

UTX is a histone demethylase gene located on the X chromosome and is a frequently mutated gene in urothelial bladder cancer (UBC). UTY is a paralog of UTX located on the Y chromosome. We performed target capture sequencing on 128 genes in 40 non-metastatic UBC patients. UTX was the most frequently mutated gene (30%, 12/40). Of the genetic alterations identified, 75% were truncating mutations. UTY copy number loss was detected in 8 male patients (22.8%, 8/35). Of the 9 male patients with UTX mutations, 6 also had copy number loss (66.7%). To evaluate the functional roles of UTX and UTY in tumor progression, we designed UTX and UTY single knockout and UTX-UTY double knockout experiments using a CRISPR/Cas9 lentiviral system, and compared the proliferative capacities of two UBC cell lines in vitro. Single UTX or UTY knockout increased cell proliferation as compared to UTX-UTY wild-type cells. UTX-UTY double knockout cells exhibited greater proliferation than single knockout cells. These findings suggest both UTX and UTY function as dose-dependent suppressors of UBC development. While UTX escapes X chromosome inactivation in females, UTY may function as a male homologue of UTX, which could compensate for dosage imbalances.
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http://dx.doi.org/10.18632/oncotarget.11207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325361PMC
September 2016

Expression patterns of GATA3 and the androgen receptor are strongly correlated in patients with triple-negative breast cancer.

Hum Pathol 2016 09 13;55:190-5. Epub 2016 May 13.

Department of Pathology, Ewha Womans University School of Medicine, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Korea. Electronic address:

GATA-binding protein 3 (GATA3) is a diagnostically useful immunohistochemical marker of breast cancer. Because of its strong association with estrogen receptor expression, GATA3 has markedly reduced sensitivity in triple-negative breast cancer (TNBC). We constructed a tissue microarray using a large series of TNBCs and evaluated GATA3 expression by TNBC subtype as defined by surrogate immunohistochemical markers. A total of 205 TNBCs were classified into cancers of the molecular apocrine type (n=23, 11.2%), claudin-low type (n=21, 10.2%), basal-like type (n=91, 44.4%), mixed type (n=62, 30.2%), and null type (n=8, 3.9%). The GATA3 scores (staining intensity × proportion) were categorized as negative (0), focally positive (1-10), or positive (11-300). GATA3 staining was negative in 153 cancers (74.6%), focally positive in 11 (5.4%), and positive in 41 (20.0%). The rate of focal positivity or positivity for GATA3 was significantly higher in the molecular apocrine type (73.9%, 17/23) than in other types of TNBCs (P=.001). The mean GATA3 score of molecular apocrine-type TNBC was significantly higher than that of the other types (P=.001) and differed significantly between androgen receptor (AR)-positive and AR-negative TNBCs (P<.001). In conclusion, GATA3 expression was correlated strongly with AR-positive, molecular apocrine-type TNBCs. Co-expression of AR and GATA3 is a specific feature of molecular apocrine-type TNBC, which may serve as a diagnostic aid for cancer of unknown primary.
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http://dx.doi.org/10.1016/j.humpath.2016.04.013DOI Listing
September 2016

Tailgut Cyst in a Neonate: A Case Report.

J Pathol Transl Med 2016 Jul 6;50(4):315-7. Epub 2016 Apr 6.

Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4132/jptm.2015.11.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963966PMC
July 2016

A Rare Case of Intra-Endometrial Leiomyoma of Uterus Simulating Degenerated Submucosal Leiomyoma Accompanied by a Large Sertoli-Leydig Cell Tumor.

Yonsei Med J 2016 Mar;57(2):523-6

Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.

A 50-year-old peri-menopausal woman presented with hard palpable mass on her lower abdomen and anemia from heavy menstrual bleeding. Ultrasonography showed a 13×12 cm sized hypoechoic solid mass in pelvis and a 2.5×2 cm hypoechoic cystic mass in uterine endometrium. Abdomino-pelvic computed tomography revealed a hypodense pelvic mass without enhancement, suggesting a leiomyoma of intraligamentary type or sex cord tumor of right ovary with submucosal myoma of uterus. Laparoscopy revealed a large Sertoli-Leydig cell tumor of right ovary with a very rare entity of intra-endometrial uterine leiomyoma accompanied by adenomyosis. The final diagnosis of ovarian sex-cord tumor (Sertoli-Leydig cell), stage Ia with intra-endometrial leiomyoma with adenomyosis, was made. Considering the large size of the tumor and poorly differentiated nature, 6 cycles of chemotherapy with Taxol and Carboplatin regimen were administered. There is neither evidence of major complications nor recurrence during 20 months' follow-up.
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http://dx.doi.org/10.3349/ymj.2016.57.2.523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740550PMC
March 2016
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