ANALYSIS OF P53, P21(WAF1), AND TGF-BETA-1 IN HUMAN DUCTAL ADENOCARCINOMA OF THE PANCREAS - TGF-BETA-1 PROTEIN EXPRESSION PREDICTS LONGER SURVIVAL

Loss of p53 and p21(WAF1) expression have previously been reported in pancreatic adenocarcinoma. Despite these findings in several reports o f 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 c arcinoma we sturdied the immunohistochemical expression of p53, p21(WA F1), and TGF-beta 1 proteins in 42 pancreatic adenocarcinomas of the d uctal type. The results were correlated with clinicopathologic finding s to identify the markers with prognostic significance. p53 nuclear im munoreactivity was seen in 20 (48%) of the cases, and it was strong to moderate in 14 (33%) of them. p21(WAF1) cytoplasmic positivity was fo und in 16 (38%) of the tumors, with 72% staining strong to moderate. T GF-beta 1 stained the cytoplasm of the tumor cells in 13 (31%). Of the p53-negative cases, 12 (54%) exhibited p21(WAF1) expression. In 3 (30 %) of cases, TGF-beta 1 reactivity was seen in the absence of p53 and p21(WAF1) p53 positivity identified armors of higher grade, but did no t correlate with stage or survival. TGF-beta 1 expression, however ide ntified low-grade tumors and patients with longer survival. No correla tion was found between the expression of any of these molecular marker s and smoking history. We report a significant correlation between TGF -beta 1 reactivity and low-grade tumors and between TGF-beta 1 and bet ter survival. This is a novel finding pointing to TGF-beta 1 as a poss ible new stage-independent predictor of tumor survival in pancreatic d uctal adenocarcinoma. In agreement with others, we also found p53 muta tion in 20 (48%) of the tumors.