Correlations between p53 gene mutations and histologic characteristics of pancreatic ductal carcinoma.

Objective: With the aim of improving early detection of pancreatic carcinoma, we attempted to make correlations among positive immunohistochemical detection of p53 expression, mutations in the p53 gene, and detailed histologic features of pancreatic carcinoma.

Methods: Seven cases of invasive pancreatic ductal carcinoma demonstrating p53 overexpression were analyzed. Serial 4- and 20-microm sections from paraffin blocks were used for immunodetection of p53 protein and microdissection, respectively. We used direct sequencing of polymerase chain reaction at 101 p53-positive and 10 p53-negative sites to sequence exons 5 to 8 of p53 and then analyzed these results in concert with detailed histologic features.

Results: Regardless of the degree of p53 overexpression, we detected p53 point mutations in all p53-positive lesions, including 22 noninvasive sites, 17 invasive areas, and 1 lymph node metastasis. No significant correlations were measured between specific p53 mutations and histologic features. Within individual tumors, the same p53 mutation was generally, but not always, detected in different areas in invasive and noninvasive lesions.

Conclusions: Our results demonstrate that p53 mutation is an early genetic event affecting a diversity of molecular pathways in pancreatic carcinogenesis and indicates a possibility of early diagnosis of pancreatic carcinoma by detecting a few p53-positive cells obtained from the pancreatic fluid.