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Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus?
Am J Surg Pathol. 2012 Mar; 36(3):331-42.AJ

Abstract

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.

Authors+Show Affiliations

Department of Pathology, Gastrointestinal Pathology Service, Massachusetts General Hospital, Boston, MA 02114-2696, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22261707

Citation

Khor, Tze Sheng, et al. "Divergent Expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in Dysplasia and Intramucosal Adenocarcinomas With Intestinal and Foveolar Morphology: Is This Evidence of Distinct Gastric and Intestinal Pathways to Carcinogenesis in Barrett Esophagus?" The American Journal of Surgical Pathology, vol. 36, no. 3, 2012, pp. 331-42.
Khor TS, Alfaro EE, Ooi EM, et al. Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus? Am J Surg Pathol. 2012;36(3):331-42.
Khor, T. S., Alfaro, E. E., Ooi, E. M., Li, Y., Srivastava, A., Fujita, H., Park, Y., Kumarasinghe, M. P., & Lauwers, G. Y. (2012). Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus? The American Journal of Surgical Pathology, 36(3), 331-42. https://doi.org/10.1097/PAS.0b013e31823d08d6
Khor TS, et al. Divergent Expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in Dysplasia and Intramucosal Adenocarcinomas With Intestinal and Foveolar Morphology: Is This Evidence of Distinct Gastric and Intestinal Pathways to Carcinogenesis in Barrett Esophagus. Am J Surg Pathol. 2012;36(3):331-42. PubMed PMID: 22261707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus? AU - Khor,Tze Sheng, AU - Alfaro,Eduardo E, AU - Ooi,Esther M M, AU - Li,Yuan, AU - Srivastava,Amitabh, AU - Fujita,Hiroshi, AU - Park,Youn, AU - Kumarasinghe,Marian Priyanthi, AU - Lauwers,Gregory Yves, PY - 2012/1/21/entrez PY - 2012/1/21/pubmed PY - 2012/4/10/medline SP - 331 EP - 42 JF - The American journal of surgical pathology JO - Am. J. Surg. Pathol. VL - 36 IS - 3 N2 - 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. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/22261707/Divergent_expression_of_MUC5AC_MUC6_MUC2_CD10_and_CDX_2_in_dysplasia_and_intramucosal_adenocarcinomas_with_intestinal_and_foveolar_morphology:_is_this_evidence_of_distinct_gastric_and_intestinal_pathways_to_carcinogenesis_in_Barrett_Esophagus L2 - http://dx.doi.org/10.1097/PAS.0b013e31823d08d6 DB - PRIME DP - Unbound Medicine ER -