Altered expression of DNA double-strand break detection and repair proteins in breast carcinomas

AIMS: To determine whether the expression of DNA damage detection and repair proteins is frequently altered in breast carcinomas. METHODS AND RESULTS: The expression profiles of five such proteins: ATM, p53, NBS1, MRE11 and Rad50 were analysed in 99 in-situ and invasive ductal breast carcinomas of different grades using an immunohistochemical approach, and compared with those seen in eight independent non-cancer (normal) breast samples and in the surrounding normal tissues of the breast carcinomas examined. ATM protein expression was reduced in 75% of the tumours compared with the levels found in normal tissues. Fewer tumours had reduced protein levels of the members of the MRE11, NBS1 and Rad50 (MNR) complex (31%, 46% and 28%, respectively) with p53 being over-expressed in 30%. In the majority of tumours (92%) we observed a good correlation between the expression of the three proteins of the MNR complex with low NBS1, MRE11 or Rad50 expression rarely found alone, suggesting that this event occurs subsequently to the deregulation in expression of other DNA repair proteins. CONCLUSION: The pattern of protein changes observed supports our hypothesis that alterations in DNA double-strand break repair capacity are involved in mammary carcinogenesis.