Microvessel density, proliferating activity, p53 and bcl-2 expression in in situ ductal carcinoma of the breast

Anticancer Res. Jul-Aug 1999;19(4B):3269-74.


Background: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of lesions that show important differences in biologic behavior. New vessel formation has been reported as a prognostic indicator in breast carcinoma, but little information is available about its significance in DCIS. This study was planned to examine angiogenesis in DCIS in relation to histologic subtype, proliferation activity, p53 and bcl-2 expression.

Materials and methods: Paraffin sections from 24 cases of DCIS (9 comedo and 15 non comedo type) were studied immunohistochemically using polyclonal and monoclonal antibodies to von Willebrand factor, Ki-67, p53 (clone 1801) and bcl-2 proteins. The streptavidine-biotin technique with microwave antigen retrieval was employed.

Results: Most cases showed enhanced microvessel formation around ducts with DCIS compared to normal ducts. Comedo carcinomas (CCs) showed enhanced neovascularization compared to non comedo carcinomas (NCCs). Growth fraction determination with Ki-67 antibody showed that 78% of the CCs expressed high proliferating activity compared to 27% of the NCCs. p53 immunoexpression was noted in 78% of the CCs and 20% of the NCCs. Bcl-2 immunoreactivity was observed in 67% of the total cases in 58% of which there was no association with p53 expression. However, an association was found between neovascularization and overexpression of Ki-67 and p53.

Conclusions: This study suggests that neovascularization is an early phenomenon in breast neoplasia and is apparent as early as the in situ stage. CCs express a more aggressive immunophenotype, compared to the other DCIS subtypes, characterized by increased stromal interaction, high proliferating activity, p53 overexpression and a near lack of bcl-2 immunostaining.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma in Situ / blood supply
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Ductal, Breast / blood supply*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cell Division*
  • Female
  • Humans
  • Middle Aged
  • Neovascularization, Pathologic
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Tumor Suppressor Protein p53 / genetics*


  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53