Implications of enhancer of zeste homologue 2 expression in pancreatic ductal adenocarcinoma

Adam D. Toll, Abhijit Dasgupta, Magdalena Potoczek, Charles J. Yeo, Celina G. Kleer, Jonathan R. Brody, Agnieszka K. Witkiewicz

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer deaths in the United States. Single-agent gemcitabine remains the standard treatment of advanced pancreatic adenocarcinoma. A recently discovered histone methyltransferase termed enhancer of zeste homologue 2 (EZH2) was found to be overexpressed in a variety of carcinomas including pancreatic adenocarcinoma. Silencing of E-cadherin was proposed as a mechanism by which enhancer of zeste homologue 2 mediates tumor aggressiveness, and enhancer of zeste homologue 2 depletion has been found to sensitize pancreatic cancer cells to gemcitabine. In this study, we correlated enhancer of zeste homologue 2 with E-cadherin expression in pancreatic adenocarcinoma and evaluated response to gemcitabine in relation to enhancer of zeste homologue 2 expression in tumor cells. Fifty-four pancreatic adenocarcinomas, 13 intraductal papillary mucinous neoplasms, and 6 chronic pancreatitis cases were stained with antibodies against enhancer of zeste homologue 2 and E-cadherin. Enhancer of zeste homologue 2 staining was scored from 1 to 4+ and classified as either low (1-2+ in <25% of tumor nuclei) or high (3-4+ in >25% of tumor nuclei). E-cadherin expression was scored on membrane positivity as follows: 0 (0%-10%), 1 (10%-25%), 2 (25%-75%), and 3 (>75%). High enhancer of zeste homologue 2 expression in pancreatic adenocarcinoma was significantly associated with decreased E-cadherin expression and more aggressive disease. There was significantly longer survival in gemcitabine-treated patients with low versus high enhancer of zeste homologue 2 expression. High enhancer of zeste homologue 2 expression was detected in intraductal papillary mucinous neoplasms with moderate to severe dysplasia, but not in chronic pancreatitis. Our study suggests that E-cadherin down-regulation may lead to enhancer of zeste homologue 2-mediated invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)1205-1209
Number of pages5
JournalHuman Pathology
Volume41
Issue number9
DOIs
StatePublished - Sep 2010

Fingerprint

Adenocarcinoma
gemcitabine
Cadherins
Neoplasms
Chronic Pancreatitis
Enhancer of Zeste Homolog 2 Protein
Pancreatic Neoplasms
Cause of Death
Down-Regulation
Staining and Labeling
Neoplasm Metastasis
Membranes
Survival
Antibodies

Keywords

  • EZH2
  • Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Implications of enhancer of zeste homologue 2 expression in pancreatic ductal adenocarcinoma. / Toll, Adam D.; Dasgupta, Abhijit; Potoczek, Magdalena; Yeo, Charles J.; Kleer, Celina G.; Brody, Jonathan R.; Witkiewicz, Agnieszka K.

In: Human Pathology, Vol. 41, No. 9, 09.2010, p. 1205-1209.

Research output: Contribution to journalArticle

Toll, Adam D. ; Dasgupta, Abhijit ; Potoczek, Magdalena ; Yeo, Charles J. ; Kleer, Celina G. ; Brody, Jonathan R. ; Witkiewicz, Agnieszka K. / Implications of enhancer of zeste homologue 2 expression in pancreatic ductal adenocarcinoma. In: Human Pathology. 2010 ; Vol. 41, No. 9. pp. 1205-1209.
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