p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer

Histopathology. 2005 Nov;47(5):458-66. doi: 10.1111/j.1365-2559.2005.02249.x.

Abstract

Aims: To study the expression of p63, cytokeratin (CK) 5 and CK8/18 in invasive ductal carcinomas and their relationship with BRCA1 and other pathological and immunohistochemical features of clinical significance.

Methods and results: Immunohistochemistry with the antibodies p63, CK5, CK8/18, BRCA1, oestrogen receptor, progesterone receptor, p53, c-erbB-2 and Ki67 was performed in 102 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. The CK5+ cases were submitted to a double-immunolabelling study with p63. There was a strong relationship between CK5 and p63 expression and both markers were associated with hormonal receptor-negative high-grade carcinomas with high proliferative rate. Furthermore, there was coexpression of CK5 and p63 in neoplastic cells, indicating that p63, like CK5, is a marker of the basal phenotype of breast cancer. There was a strong relationship between reduced expression of BRCA1 with both p63 and CK5 expression as well as an inverse correlation between p63 and CK8/18 expression, suggesting that loss of p63 expression is required for the transition between a basal to a luminal phenotype of breast carcinoma.

Conclusions: Since p63 is thought to be a marker of stem cells and may act as an oncogene, our data support the idea that BRCA1 acts as stem cell regulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / biosynthesis*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • DNA-Binding Proteins
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Keratins / biosynthesis*
  • Middle Aged
  • Phosphoproteins / biosynthesis*
  • Trans-Activators / biosynthesis*
  • Transcription Factors
  • Tumor Suppressor Proteins

Substances

  • BRCA1 Protein
  • DNA-Binding Proteins
  • Phosphoproteins
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Keratins