Expression of c-erbB2, cyclin D1 and estrogen receptor and their clinical implications in the invasive ductal carcinoma of the breast

Jpn J Clin Oncol. 2007 Sep;37(9):708-14. doi: 10.1093/jjco/hym082.

Abstract

Background: C-erbB2 and estrogen receptors (ER) are well known for their cell proliferative capacity. Cyclin D1 is a major downstream target of both c-erbB2 and ER. This study was designed to analyze the expression of c-erbB2, cyclin D1 and ER and their prognostic implications in invasive ductal carcinoma of the breast.

Methods: The c-erbB2 status was evaluated by fluorescence in situ hybridization and immunohistochemistry (IHC) and cyclin D1 and ER were evaluated by IHC in 333 invasive breast cancer specimens.

Results: The results of FISH and IHC for c-erbB2 showed 86.7% concordance. The overexpression of c-erbB2 was associated with the high expression of cyclin D1 and the negative expression of ER (P < 0.01 for both). The high expression of cyclin D1 was associated with the positive expression of ER (P < 0.01). When the group of patients who overexpressed c-erbB2 were analyzed, the patients with the low expression of cyclin D1 showed a significantly higher mortality than those with the high expression of cyclin D1 (RR = 3.2; 95% CI, 1.6-6.6). When the group of the high cyclin D1 expression was analyzed, the patients with negative expression of ER showed a significantly higher mortality than those with the positive expression of ER (RR = 2.1; 95% CI, 1.1-3.8).

Conclusions: Higher expression of cyclin D1 was associated with better prognosis in patients with c-erbB2 overexpression, and positive expression of ER was associated with better prognosis in patients with high cyclin D1 expression.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / surgery
  • Cyclin D1 / metabolism*
  • Down-Regulation
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Survival Analysis
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Cyclin D1
  • Receptor, ErbB-2