Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer

Jordan M. Winter, Angela H. Ting, Felip Vilardell, Eike Gallmeier, Steve B. Baylin, Ralph H. Hruban, Scott E. Kern, Christine A. Iacobuzio-Donahue

Research output: Contribution to journalArticlepeer-review


Purpose: The role of E-cadherin in carcinogenesis is of great interest, but few studies have examined its relevance to pancreatic carcinoma. Experimental Design: We evaluated E-cadherin protein expression by immunohistochemistry in pancreatobiliary cancers having a noncohesive histologic phenotype (21 undifferentiated adenocarcinomas and 7 signet ring carcinomas), comparing the results with pancreatic cancers having a cohesive phenotype (25 moderately differentiated and 14 poorly differentiated adenocarcinomas). Results: Twenty of 21 undifferentiated cancers had complete absence of E-cadherin expression, as did two signet ring carcinomas. In contrast, cohesive cancers (n = 39) had E-cadherin labeling at the plasma membrane (P < 0.001). Subsets of cancers were also evaluated for β-catenin expression. All of the cohesive lesions (n = 28) showed a membranous β-catenin expression pattern, whereas noncohesive foci (n = 7) were characterized by either cytoplasmic labeling or complete absence of β-catenin protein expression, suggestive of a deficient zonula adherens in noncohesive cancers. E-cadherin promoter hypermethylation was observed in an undifferentiated pancreatic cancer cell line, MiaPaCa-2, whereas two pancreatic cancer cell lines derived from differentiated lesions lacked any evidence of E-cadherin promoter methylation. No pattern of E-cadherin promoter methylation could be determined in three primary cancers having mixed histologic patterns (contained both cohesive and noncohesive foci). No somatic mutations in E-cadherin were identified in noncohesive pancreatic cancers having inactivated E-cadherin. Conclusions: Noncohesive pancreatic cancers were characterized by the loss of E-cadherin protein expression. Promoter hypermethylation is a possible mechanism of E-cadherin gene silencing in a subset of these cancers.

Original languageEnglish (US)
Pages (from-to)412-418
Number of pages7
JournalClinical Cancer Research
Issue number2
StatePublished - Jan 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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