title: bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome.
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.
authors.affiliation: Departments of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Sinicrope
authors.forename: D B
authors.initials: DB
authors.lastname: Evans
authors.forename: S D
authors.initials: SD
authors.lastname: Leach
authors.forename: K R
authors.initials: KR
authors.lastname: Cleary
authors.forename: C J
authors.initials: CJ
authors.lastname: Fenoglio
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: J L
authors.initials: JL
authors.lastname: Abbruzzese
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53