ATM gene expression is associated with differentiation and angiogenesis in infiltrating breast carcinomas

Abstract

The product of the ATM gene, mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a key role in the detection and repair of DNA doublestrand breaks. A-T is defined by progressive cerebellar ataxia, telangiectasia, sensitivity to ionising radiation and genomic instability with cancer predisposition. On the other hand, increased angiogenesis is essential for tumor growth and metastasis. The aim of this study was to investigate ATM expression in breast carcinomas and its relationship to neoangiogenesis. Methods and Results: Fifty-two breast tumors from 51 patients, 38 of them with concomitant in situ component (CIS), were analyzed by immunohistochemistry for the expression of ATM. CD34 expression was used for the morphometric evaluation of vasculature. ATM was positive in 1 to 10% of normal epithelial cells. ATM expression was reduced in 55.8% of infiltrating carcinomas, non-reduced in 34.6%, and increased in 9.6%. Expression of ATM in CIS was similar to the infiltrating component in 71% of cases and reduced in 23.7% of them. High-grade ductal infiltrating carcinomas showed lower ATM expression than lowgrade ones. Reduced ATM expression also correlated with increased microvascular area. Conclusions: Reduced ATM expression in breast carcinomas correlated with tumor differentiation and increased microvascular parameters, supporting its role in neoangiogenesis and tumor progression in breast carcinogenesis.