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Annals of Surgical Oncology 10:284-290 (2003)
© 2003 Society of Surgical Oncology

ORIGINAL ARTICLES

Dysregulation of ß-Catenin Expression Correlates With Tumor Differentiation in Pancreatic Duct Adenocarcinoma

Andrew M. Lowy, MD, Cecilia Fenoglio-Preiser, MD, On Ja Kim, MD, Jennifer Kordich, MS, Ana Gomez, MD, Joy Knight, MS, Laura James, MS and Joanna Groden, PhD

From the Department of Surgery, Division of Surgical Oncology (AML, JJK, JK, LJ), the Department of Pathology and Laboratory Medicine (OJK, AG, CF-P), and the Department of Molecular Genetics, Biochemistry and Microbiology, Howard Hughes Medical Institute (JG), University of Cincinnati College of Medicine, Cincinnati, Ohio.

Correspondence: Address correspondence and reprint requests to: Andrew M. Lowy, MD, Division of Surgical Oncology, University of Cincinnati, 234 Goodman Street, Cincinnati, OH 45219-0772; Fax: 513-584-0459; E-mail: lowyam{at}healthall.com

Background: ß-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. ß-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered ß-catenin expression in numerous tumor types; however, reports regarding ß-catenin expression in pancreatic cancer have been conflicting.

Methods: ß-Catenin expression was examined in 10 pancreatic cancer cell lines by Western and Northern analysis and by immunofluorescence. Expression was also examined by immunohistochemistry in 57 primary pancreatic cancers and 7 foci of carcinoma-in-situ.

Results: Reduced expression of ß-catenin was observed in 4 of 10 pancreatic cancer cell lines. Reduced membranous expression was noted in 32 pancreatic cancers (56%) and correlated with loss of tumor differentiation. Nuclear ß-catenin expression was identified in two tumors (4%). ß-Catenin expression was present in all seven foci of carcinoma-in-situ; however, nuclear expression was predominant in four of the seven cases.

Conclusions: Alterations in ß-catenin expression are common in pancreatic cancer; however, signaling and adhesion functions may be perturbed at different times during tumor progression. Therefore, dysregulation of ß-catenin may contribute to the development and progression of this disease through distinct mechanisms.

Key Words: ß-Catenin • Pancreatic cancer • E-cadherin • Adhesion • Wnt signaling




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[Abstract] [Full Text] [PDF]


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