Analysis of p53, p21WAF1, and TGF-β1 in human ductal adenocarcinoma of the pancreas -: TGF-β1 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 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 sturdied the immunohistochemical expression of p53, p21(WAF1), and TGF-beta 1 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. p21(WAF1) cytoplasmic positivity was found in 16 (38%) of the tumors, with 72% staining strong to moderate. TGF-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 not correlate with stage or survival. TGF-beta 1 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-beta 1 reactivity and low-grade tumors and between TGF-beta 1 and better survival. This is a novel finding pointing to TGF-beta 1 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.