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Kim, Dae Hwan,Shin, Nari,Kim, Gwang Ha,Song, Geum Am,Jeon, Tae-Yong,Kim, Dong-Heon,Lauwers, Gregory Y,Park, Do Youn American Medical Association 2013 Archives of pathology & laboratory medicine Vol.137 No.8
<P>The clinical validity of mucin expression in gastric cancer is debated. Whereas several reports demonstrate a correlation between mucin expression and prognosis, others deny such an association.</P>
강현정 ( Hyun Jeong Kang ),박도윤 ( Do Youn Park ),김광하 ( Kwang Ha Kim ),송근암 ( Geun Am Song ),( Gregory Y Lauwers ) 대한소화기학회 2008 대한소화기학회지 Vol.52 No.5
Gastric epithelial neoplasia is a very common disease entity in Korea, encompassing gastric adenoma and adenocarcinoma. There are still discrepancies in pathologic diagnosis of gastric epithelial neoplasia between Western and Japanese pathologists after Vienna consensus classification. With increasing use of endoscopic therapy such as endoscopic mucosal resection and endoscopic submucosal dissection, it is very important to agree on the consensus criteria in the diagnosis of gastric epithelial neoplasia among pathologists in Korea. On this background, the current concepts, and contemporary issues of definition, diagnostic and classification criteria of gastric epithelial neoplasia were reviewed. (Korean J Gastroenterol 2008;52:273-280)
Ahn, Sangjeong,Lee, So-Jeong,Kim, Yonugkeum,Kim, Ahrong,Shin, Nari,Choi, Kyung Un,Lee, Chang-Hun,Huh, Gi Yeong,Kim, Kyong-Mee,Setia, Namrata,Lauwers, Gregory Y.,Park, Do Youn Wolters Kluwer Health, Inc. All rights reserved. 2017 The American journal of surgical pathology Vol.41 No.1
<P>Gastric cancers have recently been classified into several types on the basis of molecular characterization, and the new taxonomy has shown to have clinical relevance. However, the technology required for thorough molecular classification is complicated and expensive, currently preventing widespread use. We aimed to reproduce the results of molecular classification using only simple techniques, that is, immunohistochemical analysis and in situ hybridization. We classified a cohort of 349 successive gastric adenocarcinomas into 5 subtypes, on the basis of protein or mRNA expression of MLH1, E-cadherin, p53, and Epstein-Barr virus. We observed that the subtypes presented distinct clinicopathologic characteristics and corresponded to the molecular classifications previously reported. Epstein-Barr virus-positive tumors were more common in male individuals and in the body of the stomach. Microsatellite-unstable (MSI) tumors, which showed aberrant MLH1 expression, were correlated with increased age and intestinal histology. Both types showed better overall survival than the other types. Gastric cancers with reduced expression of E-cadherin, corresponding to the epithelial to mesenchymal transition or genome stable subtypes, showed the poorest overall survival, with a high prevalence of poorly cohesive carcinoma (ie, diffuse type, of the Lauren classification system). In conclusion, we were able to reproduce a previously reported molecular classification of gastric cancers using immunohistochemical analysis and in situ hybridization. We verified the effectiveness and applicability of this method, which shows promise for use in a clinical setting in the foreseeable future.</P>
Pyloric Gland Adenoma in Lynch Syndrome
Lee, Seung Eun,Kang, So Young,Cho, Junhun,Lee, Boram,Chang, Dong Kyung,Woo, Hyein,Kim, Jong Won,Park, Ha Young,Do, In Gu,Kim, Young Eun,Kushima, Ryoji,Lauwers, Gregory Y.,Park, Cheol Keun,Kim, Kyoung Raven Press 2014 The American journal of surgical pathology Vol.38 No.6
<P>The prevalence of gastric cancer associated with Lynch syndrome (LS) is highly variable, and the underlying histologic pathway or molecular mechanisms remain unclear. From 1995 to 2012, 15 patients had been treated for both gastric and colonic adenocarcinomas and diagnosed as LS. In all cases, pathologic review, immunohistochemical analysis for mismatch-repair proteins, and microsatellite instability (MSI) tests were performed. To confirm LS, germline mutation tests and multiplex ligation-dependent probe amplification were performed. All gastric and colonic carcinomas were MSI-high and lost expressions of MLH1/PMS2 in 11 (73%) cases and MSH2/MSH6 in 4 (27%) cases. Remarkably, in a patient with LS and germline mutation of <I>MLH1</I> gene, pyloric gland adenoma (PGA) transformed to adenocarcinoma during follow-up. In 2 additional cases, PGA was found adjacent to advanced gastric cancers. All PGAs in LS patients were MSI-high and lost expression of mismatch-repair proteins (MLH1/PMS2 in 2 cases and MSH2/MSH6 in 1 case), whereas none of the 14 sporadic PGAs was MSI-high or had lost expression of mismatch-repair proteins. On the basis of these observations, although very rare, we suggest the possibility that PGA may be a precursor lesion to gastric adenocarcinoma in LS and that the mismatch-repair deficient pathway of carcinogenesis is involved early in the gastric carcinogenesis pathway.</P>
Khor, Tze Sheng,Alfaro, Eduardo E.,Ooi, Esther M. M.,Li, Yuan,Srivastava, Amitabh,Fujita, Hiroshi,Park, Youn,Kumarasinghe, Marian Priyanthi,Lauwers, Gregory Yves Lippincott Williams Wilkins, Inc. 2012 The American journal of surgical pathology Vol.36 No.3
Dysplasia in Barrett esophagus has been recognized to be morphologically heterogenous, featuring adenomatous, foveolar, and hybrid phenotypes. Recent studies have suggested a tumor suppressor role for CDX-2 in the metaplasia-dysplasia-carcinoma sequence. The phenotypic stability and role of CDX-2 in the neoplastic progression of different types of dysplasias have not been evaluated. Thirty-eight endoscopic mucosal resections with dysplasia and/or intramucosal carcinoma (IMC) arising in Barrett esophagus were evaluated for the expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2. The background mucosa was also evaluated. The results were correlated with morphologic classification and clinicopathologic parameters. Of 38 endoscopic mucosal resections, 23 had IMC and dysplasia, 8 had IMC only, and 7 had dysplasia only. Among dysplastic lesions, 73% were foveolar, 17% were adenomatous, and 10% were hybrid. Twenty of 23 cases with dysplasia and adjacent IMC showed an identical immunophenotype of dysplasia and IMC comprising 16 gastric, 3 intestinal, and 1 mixed immunophenotype. Three cases showed discordance of dysplasia and IMC immunophenotype. These findings suggest that most Barrett-related IMC cases are either gastric or intestinal, with phenotypic stability during progression supporting separate gastric and intestinal pathways of carcinogenesis. CDX-2 showed gradual downregulation of expression during progression in adenomatous dysplasia but not in foveolar or hybrid dysplasia, supporting a tumor suppressor role, at least in the intestinal pathway. CDX-2 was also found to be expressed to a greater degree in intestinal metaplasia compared with nonintestinalized columnar metaplasia. Consistent with CDX-2 as a tumor suppressor, this suggests that nonintestinalized columnar metaplasia may be an unstable intermediate state at risk for neoplastic progression.