C-kit overexpression correlates with KIT gene copy numbers increases in phyllodes tumors of the breast

Breast Cancer Res Treat. 2015 Jan;149(2):395-401. doi: 10.1007/s10549-014-3214-1. Epub 2014 Dec 23.

Abstract

We determined c-kit expression in the stroma and epithelia of benign, borderline, and malignant phyllodes tumors (PTs), respectively, as well as the relationship between c-kit expression in stromal elements and KIT gene copy number variations (CNVs). To assess c-kit expression and KIT CNVs, 348 PT cases were studied: 120 (34.4 %) benign cases, 115 (33.1 %) borderline cases, and 113 (32.5 %) malignant cases. All of these cases were evaluated for c-kit (CD117) expression using immunohistochemistry. Forty-two cases (29 c-kit-positive in the stromal cells cases and 13 negative cases) were investigated for KIT gene CNVs via genomic polymerase chain reaction (PCR). The overall rate of c-kit positivity in the stroma was 46.8 %, as well as 24.2, 53.1, and 64.6 %, respectively, in PTs of three different grades. However, in the majority of cases, the epithelia were c-kit positive (98.2 %), and the positivity was 100, 99.1, and 95 % in PTs of three different grades, respectively. There was a significant change in the expression of c-kit in the stroma and epithelia according to grade (P < 0.001, P = 0.014). From the genomic PCR results, we can confirm that c-kit positivity in the stroma is directly correlated with KIT gene copy numbers increases (P = 0.003, P = 0.041). We demonstrated that c-kit expression in the stroma of PTs is positively associated with malignancy. c-Kit epithelial positivity was inversely correlated with PTs malignancy. c-Kit overexpression in the stroma was related to KIT gene copy numbers increases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Child
  • DNA Copy Number Variations
  • Exons
  • Female
  • Gene Dosage*
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading
  • Phyllodes Tumor / genetics*
  • Phyllodes Tumor / metabolism
  • Phyllodes Tumor / pathology
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-kit / genetics*
  • Young Adult

Substances

  • Proto-Oncogene Proteins c-kit