Expression of death-related genes and their relationship to loss of apoptosis in T1 ductal breast carcinomas

Abstract

Expression of the death-related proteins (DRPs) Bcl-2, Bax, Bcl-x and Bak that regulate cell survival and death was examined using immuno-histochemical methods in a group of 142 T1 (<2 cm) ductal breast carcinomas. Immunostaining results were correlated with loss of apoptosis and clinicopathological parameters such as histological grade (HG) and lymph node involvement. Expression of anti-apoptotic proteins Bcl-2 and Bcl-x was found in 57.0% and 62.75% of tumors, respectively. Bcl-2 expression, but not Bcl-x expression, was related to loss of apoptosis. Expression of the apoptotic proteins Bax and Bak was present in 58% of Bcl-2-negative tumors and associated significantly with an increase in apoptosis. Expression of these DRPs was associated significantly with the HG of the tumors: Bcl-2 and Bak expression was predominant in HG I/II tumors, whereas expression of Bcl-xL and Bax was commonly observed in HG III tumors, as occurs for p53 over-expression. Our results suggest that the loss or gain of apoptosis is regulated tightly in T1 breast carcinomas through the expression of different effectors along with tumor cell differentiation.