title: MUC2 expression is an adverse prognostic factor in superficial gastroesophageal adenocarcinomas.
abstract: 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 (eg, 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 (hazard ratio 2.2, 95% confidence interval 1.2-4.2), independent of node stage and other prognostic factors. MUC2 expression in submucosal EAC also showed significantly accelerated time to recurrence (hazard ratio 2.8, 95% confidence interval 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.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Presbyterian University Hospital A610, Pittsburgh, PA 15213. Electronic address: davisonjm@upmc.edu.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Davison
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
authors.forename: Shane T
authors.initials: ST
authors.lastname: Ellis
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Presbyterian University Hospital A610, Pittsburgh, PA 15213.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Foxwell
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
authors.forename: James D
authors.initials: JD
authors.lastname: Luketich
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gibson
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Presbyterian University Hospital A610, Pittsburgh, PA 15213.
authors.forename: Shih-Fan
authors.initials: SF
authors.lastname: Kuan
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
authors.forename: Katie S
authors.initials: KS
authors.lastname: Nason
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004943:Esophagogastric Junction / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D018396:Mucin-1 / Q000378:metabolism; D055262:Mucin-2 / Q000378:metabolism*; D055272:Mucin-6 / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C524625:MUC2 protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D055272:Mucin-6
keywords: Esophagus; Glandular and epithelial neoplasms; MUC2 protein; Mucins; Survival