Roles of mismatch repair proteins hMSH2 and hMLH1 in the development of sporadic breast cancer

Hiroaki Murata, Nada H. Khattar, Liya Gu, Guo Min Li

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Defects in mismatch repair (MMR) genes, particularly the hMSH2 and hMLH1 genes, are associated with a variety of cancers including sporadic breast cancer. However, whether or not patient clinical background, e.g. age, progesterone receptor (PR), estrogen receptor (ER), tumor progression and stage, chemotherapy history, and menopausal status, influences MMR status is not understood. To address these issues, 83 archival breast cancer specimens were examined for expression of hMSH2 and hMLH1 by immunohistochemistry and the relationship between MMR protein expression and patient clinical background was analyzed. We detected lack of or reduced expression of hMSH2 and hMLH1 in 23 (27.7%) and 26 cases (31.3%), respectively, and hypermethylation of the hMLH1 promoter accounted for the majority of the cases with reduced expression of hMLH1. Statistical analysis revealed that (i) reduced expression of hMLH1 and hMSH2 seemed to confer advantage for the progression of breast tumors to more advanced stages; (ii) attenuated expression of hMLH1 correlated with history of chemotherapy, but not with age, menopause, or the status of PR and ER; (iii) hypermethylation of the hMLH1 promoter was linked with clinical stage and lymphatic metastasis. These analyses indicate that defective expression of MMR genes is closely associated with the development of sporadic breast cancer.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalCancer Letters
Volume223
Issue number1
DOIs
StatePublished - Jun 1 2005

Keywords

  • Breast cancer
  • MMR
  • Methylation
  • Protein expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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