Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

Szachnowicz, Sérgio; Cecconello, Ivan; Ribeiro, Ulysses; Iriya, Kiyoshi; Ibrahim, Roberto El; Takeda, Flávio Roberto; Corbett, Carlos Eduardo Pereira; Safatle‐Ribeiro, Adriana Vaz

doi:10.1186/1477-7819-7-27

Cited by 14 publications

(10 citation statements)

References 30 publications

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“…Prior studies have illustrated that mucin core proteins are expressed in EAC (5, 26–29), but our study is the first to explore the prognostic significance of subclassifying superficial EAC based on the pattern of MUC protein expression.…”

Section: Discussionmentioning

confidence: 97%

MUC2 expression is an adverse prognostic factor in superficial gastroesophageal adenocarcinomas

et al. 2014

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Mucin core proteins (MUCs) are expressed in tissue specific patterns in the gastrointestinal tract and expression is deregulated in Barrett’s metaplasia. Based on differential expression, MUCs have been used to classify adenocarcinomas into distinct phenotypes (e.g. intestinal, gastric, pancreaticobiliary, etc). Because MUC expression patterns carry prognostic significance in other tumors, we evaluated MUC expression in superficial adenocarcinomas of the gastroesophageal junction and esophagus (EAC) to determine whether there are differences in outcome associated with MUC subtype in this potentially curable subset of EAC. We classified 142 resected, superficial (T1) EAC based on their pattern of expression of MUC2, MUC5AC, MUC6 and MUC1. The association between survival and MUC expression pattern was determined in univariate and multivariate analyses. The MUC2 positive “intestinal” phenotype was associated with significantly worse prognosis in submucosal EAC (HR 2.2, 95%CI 1.2–4.2), independent of node stage and other prognostic factors. MUC2 expression in submucosal EAC also showed significantly accelerated time to recurrence (HR 2.8, 95% CI 1.2–6.8) after adjusting for node stage. The classification of superficial EAC by MUC protein expression has prognostic significance. MUC2 expression is an adverse prognostic indicator in submucosal EAC, independent of node stage and other prognostic factors.

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Section: Discussionmentioning

confidence: 97%

MUC2 expression is an adverse prognostic factor in superficial gastroesophageal adenocarcinomas

et al. 2014

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“…These 2 markers have also been used to elucidate the cellular origin of adenocarcinomas arising in Barrett esophagus with MUC5AC expression more specific to gastric type adenocarcinoma and MUC2 reflective of intestinal type adenocarcinoma [9]. No expression of either marker is seen in normal squamous mucosa of the esophagus [9].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical panel for distinguishing esophageal adenocarcinoma from squamous cell carcinoma: a combination of p63, cytokeratin 5/6, MUC5AC, and anterior gradient homolog 2 allows optimal subtyping

et al. 2012

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Distinguishing adenocarcinoma and squamous cell carcinoma of the esophagus is often based on morphologic criteria and can be difficult in small biopsies. We analyzed commonly used immunohistochemical markers (p63, cytokeratin 5/6, cytokeratin 7, CDX2, MUC2, and MUC5AC) and two new markers, AGR2 and SOX2, in esophageal carcinomas to establish the best panel to distinguish these tumors. Tissue microarrays with 69 esophageal adenocarcinomas and 41 whole sections of esophageal squamous cell carcinomas were stained for these markers and semiquantitatively scored. Sensitivities and specificities were calculated for individual markers and select combinations using the morphologic diagnosis as a gold standard. All squamous cell carcinomas expressed p63 with 38/41 demonstrating reactivity in >75% of tumor cells. Cytokeratin 5/6 expression was seen in 40/41 squamous cell carcinomas with 39/41 demonstrating reactivity >75% of tumor cells. SOX2 expression was present in 35/41 of squamous cell carcinomas but also in 24/69 of adenocarcinomas, frequently demonstrating extensive reactivity in adenocarcinomas. AGR2 was highly sensitive for adenocarcinoma and present in 68/69 of cases, but AGR2 reactivity was also identified in 15/41 of squamous cell carcinomas, typically demonstrating focal reactivity in squamous cell carcinoma. MUC5AC expression was seen almost exclusively in adenocarcinomas with only a single squamous cell carcinoma demonstrating focal MUC5AC staining. Overall, the dual expression of both p63 and cytokeratin 5/6 was 99% specific and 98% sensitive for squamous cell carcinoma. In addition, AGR2 and MUC5AC are useful positive markers of adenocarcinoma in the setting of absent or diminished p63 and cytokeratin 5/6 staining.

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“…Moreover, BACs segregate into gastric-type tumors with MUC5A positivity and intestinal-type tumors with MUC2 positivity; Szachnowicz et al [41] suggested that these 2 BAC subtypes may reflect 2 different potential cells of origin being involved in BAC carcinogenesis.…”

Section: Expression Pattern Changes Associated With Be Lesionsmentioning

confidence: 99%

Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus

Ahrens

Lutz²,

Laßmann³

et al. 2016

Pathobiology

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Barrett's esophagus (BE) is defined as metaplasia of the esophageal squamous epithelium with multiple cell layers into a single layer of intestinal columnar epithelial cells - or, in other words, skyscrapers are turned into town houses. The underlying pathomechanism(s) and the cell of origin of BE lesions have not been defined yet. However, four potential hypotheses for BE development have been suggested. The morphological changes during BE development are associated with rather well-described aberrant gene/protein expression patterns. However, the potential key regulators of this conversion process are still unclear. The process of metaplastic conversion is difficult to monitor in a spatiotemporal manner in vitro, and robust models are lacking. There is therefore a need for novel experimental systems. This review focuses on potential key regulators, microenvironmental influences, epigenetic alterations and experimental research systems related to BE.

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Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

Abstract: Background: Mucin immunoexpression in adenocarcinoma arising in Barrett's esophagus (BE) may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification.

Cited by 14 publications

References 30 publications

MUC2 expression is an adverse prognostic factor in superficial gastroesophageal adenocarcinomas

MUC2 expression is an adverse prognostic factor in superficial gastroesophageal adenocarcinomas

Immunohistochemical panel for distinguishing esophageal adenocarcinoma from squamous cell carcinoma: a combination of p63, cytokeratin 5/6, MUC5AC, and anterior gradient homolog 2 allows optimal subtyping

Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus

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