bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: Association with clinical outcome

Frank A. Sinicrope, Douglas B. Evans, Steven D. Leach, Karen R. Cleary, Claudia J. Fenoglio, J. Jack Lee, James L. Abbruzzese

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Abstract

The bcl-2 proto-oncogene and the p53 tumor suppressor gene are important determinants of tumor cell susceptibility to apoptosis. bcl-2 and mutant p53 proteins inhibit apoptosis in vitro and can provide prognostic information in certain tumor types. We analyzed bcl-2 and p53 expression in archival pancreatic (n = 35) and ampullary (n = 6) adenocarcinomas, resected for cure, and their relationship to overall survival. Patients were treated with 5-fluorouracil and irradiation either pre- (n = 21) or postoperatively (n = 15); 5 patients received surgery alone. Using specific monoclonal antibodies, cytoplasmic bcl-2 and nuclear p53 proteins were detected in 22 of 40 (55%) and 20 of 37 (54%) tumors, respectively. No relationship was found between bcl-2 and p53 expression. Neither bcl-2 nor p53 correlated with histological response to preoperative chemoradiation. Lymph node involvement predicted poor overall survival (P = 0.02). A trend toward improved survival was seen in well-differentiated (P = 0.08) tumors and in those with increased bcl-2 expression (P = 0.06). p53 expression was not related to clinical outcome. In a multivariate analysis, nodal status was the single most important predictor of overall survival. Of note, the combined variable of bcl-2 expression and histological grade was a stronger prognostic variable than nodal status alone. Unlike nodal status, these features can potentially be evaluated in preoperative biopsy specimens.

Original languageEnglish (US)
Pages (from-to)2015-2022
Number of pages8
JournalClinical Cancer Research
Volume2
Issue number12
StatePublished - Dec 1 1996

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sinicrope, F. A., Evans, D. B., Leach, S. D., Cleary, K. R., Fenoglio, C. J., Lee, J. J., & Abbruzzese, J. L. (1996). bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: Association with clinical outcome. Clinical Cancer Research, 2(12), 2015-2022.