title: Analysis of p53, p21WAF1, and TGF-beta1 in human ductal adenocarcinoma of the pancreas: TGF-beta1 protein expression predicts longer survival.
abstract: Loss of p53 and p21WAF1 expression have previously been reported in pancreatic adenocarcinoma. Despite these findings in several reports of oncogene and tumor suppressor gene alterations in pancreatic cancer, the clinical significance of these changes is still poorly understood. In an attempt to detect molecular prognostic markers for pancreatic carcinoma, we studied the immunohistochemical expression of p53, p21WAF1, and TGF-beta1 proteins in 42 pancreatic adenocarcinomas of the ductal type. The results were correlated with clinicopathologic findings to identify the markers with prognostic significance. p53 nuclear immunoreactivity was seen in 20 (48%) of the cases, and it was strong to moderate in 14 (33%) of them. p21WAF1 cytoplasmic positivity was found in 16 (38%) of the tumors, with 72% staining strong to moderate. TGF-beta1 stained the cytoplasm of the tumor cells in 13 (31%). Of the p53-negative cases, 12 (54%) exhibited p21WAF1 expression. In 3 (30%) of cases, TGF-beta1 reactivity was seen in the absence of p53 and p21WAF1 p53 positivity identified tumors of higher grade, but did not correlate with stage or survival. TGF-beta1 expression, however, identified low-grade tumors and patients with longer survival. No correlation was found between the expression of any of these molecular markers and smoking history. We report a significant correlation between TGF-beta1 reactivity and low-grade tumors and between TGF-beta1 and better survival. This is a novel finding pointing to TGF-beta1 as a possible new stage-independent predictor of tumor survival in pancreatic ductal adenocarcinoma. In agreement with others, we also found p53 mutation in 20 (48%) of the tumors.
authors.affiliation: Department of Pathology, H. Lee Moffitt Cancer Center, University of South Florida College of Medicine, Tampa 33612-9497, USA.
authors.forename: D
authors.initials: D
authors.lastname: Coppola
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: J P
authors.initials: JP
authors.lastname: Fruehauf
authors.forename: A
authors.initials: A
authors.lastname: Kyshtoobayeva
authors.forename: R C
authors.initials: RC
authors.lastname: Karl
authors.forename: S V
authors.initials: SV
authors.lastname: Nicosia
authors.forename: T J
authors.initials: TJ
authors.lastname: Yeatman
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53