c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer

Br J Surg. 2013 Mar;100(4):490-6. doi: 10.1002/bjs.9021. Epub 2013 Jan 14.

Abstract

Background: As patients with basal-like breast cancer (BLBC) have a poor prognosis and there is no specifically tailored therapy, molecular biological characterization of BLBC is necessary. c-Kit is a transmembrane receptor tyrosine kinase known to play important roles in various solid cancers. This study classified BLBCs from patients with breast carcinoma, and addressed the significance of c-Kit expression in these tumours.

Methods: Primary breast tumours were stained with antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor (HER) 2, epidermal growth factor receptor (EGFR), cytokeratin 5/6 and c-Kit. The association between c-Kit, BLBC and survival was analysed.

Results: A total of 667 patients with breast cancer were followed up for a median of 39 (range 6-72) months. Some 190 tumours (28·5 per cent) were classified as triple-negative for breast cancer (negative for oestrogen receptor, progesterone receptor and HER2) and 149 (78·4 per cent) had characteristics of BLBC (positive for cytokeratin 5/6 and/or EGFR). c-Kit expression was detected in 111 (16·6 per cent) of 667 tumours. c-Kit-positive tumours were more commonly found among patients with BLBC (42 of 149, 28·2 per cent; P < 0·001) and in patients with nodal metastasis (47 of 216, 21·8 per cent; P = 0·014) than in those without. In patients with BLBC, the prognosis was significantly worse in those with c-Kit expression (P < 0·001). Multivariable logistic regression analysis revealed c-Kit as an independent negative prognostic factor for cancer-specific survival in patients with BLBC (hazard ratio 2·29, 95 per cent confidence interval 1·11 to 4·72).

Conclusion: c-Kit might be a prognostic marker and possible molecular target for therapy in patients with BLBC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / mortality*
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality*
  • Carcinoma, Ductal, Breast / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Receptors, Progesterone
  • Proto-Oncogene Proteins c-kit
  • Receptor, ErbB-2