Angiogenesis and p53 and H-ras mutations in pancreatic ductal adenocarcinoma

OBJECTIVE: To evaluate the correlation of angiogenesis and p53 and H-ras mu tations with prognostic factors and proliferative activity assessed with Ki -67 protein expression by studying archival tissues from 24 patients with p rimary pancreatic ductal adenocarcinoma. STUDY DESIGN: Vascular structures were labeled immunohistochemically using factor VIII-related antigen. Vascular surface density (VSD) and microvessel number (NVES) were assessed by stereology. The tissues were also analyzed with the immunohistochemical method for the expression of proteins, includi ng p53, H-ras and Ki-67. RESULTS: Statistical analysis revealed that tumors with greater NVES and VS D values significantly correlated with occurence of metastases, higher prol iferative activity, poorer histologic differentiation and greater tumor siz e. p53 Mutations were found in II cases (45.8%). However, only three cases (12.5%), all negative for p53 mutations, showed H-ras mutations, p53 Mutati on-positive tumors exhibited a statistically significant correlation with o ccurrence of metastases and higher proliferative activity, whereas H-ras mu tations did not show such a correlation. CONCLUSION: Angiogenesis might have a role in predicting prognosis in pancr eatic carcinomas, and p53 mutations might be acquired in later stages assoc iated with metastatic progression and higher proliferative activity. Althou gh H-ras mutations were rare in the present study, they might play a role i n a different carcinogenic pathway excluding p53 mutations.