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

Anal Quant Cytol Histol. 1999 Dec;21(6):473-6.

Abstract

Objective: To evaluate the correlation of angiogenesis and p53 and H-ras mutations with prognostic factors and proliferative activity assessed with Ki-67 protein expression by studying archival tissues from 24 patients with primary 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, including p53, H-ras and Ki-67.

Results: Statistical analysis revealed that tumors with greater NVES and VSD values significantly correlated with occurrence of metastases, higher proliferative activity, poorer histologic differentiation and greater tumor size. p53 Mutations were found in 11 cases (45.8%). However, only three cases (12.5%), all negative for p53 mutations, showed H-ras mutations. p53 Mutation-positive tumors exhibited a statistically significant correlation with occurrence of metastases and higher proliferative activity, whereas H-ras mutations did not show such a correlation.

Conclusion: Angiogenesis might have a role in predicting prognosis in pancreatic carcinomas, and p53 mutations might be acquired in later stages associated with metastatic progression and higher proliferative activity. Although H-ras mutations were rare in the present study, they might play a role in a different carcinogenic pathway excluding p53 mutations.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Ductal, Breast / blood supply*
  • Carcinoma, Ductal, Breast / chemistry
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neovascularization, Pathologic / genetics*
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Tumor Suppressor Protein p53
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)