Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients

Int J Cancer. 2005 Feb 10;113(4):575-80. doi: 10.1002/ijc.20638.

Abstract

The CHEK2 kinase is a tumor suppressor whose activation in response to DNA double-strand breaks contributes to cell cycle arrest or apoptosis. The c.1100delC mutation is associated with familial breast cancer, and tumors from mutation carriers show reduced or absent CHEK2 protein expression. We have here studied CHEK2 protein expression by immunohistochemistry on a tissue microarray of 611 unselected breast tumors and also evaluated the tumor characteristics among 1,297 unselected breast cancer patients defined for the c.1100delC germ line mutation status (2.5% carrier frequency). CHEK2 protein expression was reduced in 21.1% of the unselected breast cancers studied. Tumors with reduced CHEK2 expression had more often larger primary tumor size (pT3-4; nominal significance p = 0.002) compared to tumors with normal staining. A similar trend for larger tumor size was seen among the 37 breast tumors from c.1100delC germ line mutation carriers. Tumors from c.1100delC mutation carriers were of higher grade than those of noncarriers (nominal significance p = 0.02). The c.1100delC germ line mutation also associated strongly with bilateral breast cancer. No significant correlation was seen between CHEK2 status and hormone receptor status, histology, lymph node status, or overall survival.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal / genetics
  • Carcinoma, Ductal / metabolism
  • Carcinoma, Ductal / pathology
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / metabolism
  • Carcinoma, Medullary / pathology
  • Checkpoint Kinase 2
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Germ-Line Mutation*
  • Humans
  • Immunoenzyme Techniques
  • Lymph Nodes / pathology
  • Neoplasm Staging
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Sequence Deletion
  • Survival Rate
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases