Bcl-2 protein expression in breast cancer in relation to established prognostic factors and other clinicopathological variables*

BACKGROUND:: Bcl-2 inhibits most kinds of programmed cell death and providesa selective survival advantage to various cell types. Bcl-2is physiologically expressed in ductal epi-thelia of the normalbreast. The biological significance of Bcl-2 (over)expressionfor the development and progression of breast cancer has stillto be evaluated. PATIENTS AND METHODS:: A series of 133 primary breast cancers was investigated forexpression of the Bcl-2 protein by immunohistochemistry of paraffin-embeddedtissue sections. Results were correlated with other variablesof established or presumed predictive value. RESULTS:: A significant positive correlation was observed between Bcl-2expression and positivity for estrogen and progesterone receptors(p < 0.001). High proliferative activity as assessed by Ki-67staining correlated inversely with Bcl-2 expression (p <0.001). Bcl-2 immunostaining was not related to positivity forc-erbB-1. It was negatively associated with overexpression ofc-erbB-2 (p = 0.04), whereas a strong positive correlation wasfound with expression of c-erbB-3 (p = 0.01). There was a significantinverse correlation between histological grading and immunoreactivityfor Bcl-2 (p < 0.001). No tumors tended to be Bcl-2 positive,but differences were not statistically significant.Background:Bcl-2 inhibits most kinds of programmed cell death and providesa selective survival advantage to various cell types. Bcl-2is physiologically expressed in ductal epi-thelia of the normalbreast. The biological significance of Bcl-2 (over)expressionfor the development and progression of breast cancer has stilto be evaluated. PATIENTS AND METHODS:: A series of 133 primary breast cancers was investigated forexpression of the Bcl-2 protein by immunohistochemistry of paraffin-embeddedtissue sections. Results were correlated with other variablesof established or presumed predictive value. RESULTS:: A significant positive correlation was observed between Bcl-2expression and positivity for estrogen and progesterone receptors(p < 0.001). High proliferative activity as assessed by Ki-67staining correlated inversely with Bcl-2 expression (p <0.001). Bcl-2 immunostaining was not related to positivity forc-erbB-1. It was negatively associated with overexpression ofc-erbB-2 (p = 0.04), whereas a strong positive correlation wasfound with expression of c-erbB-3 (p — 0.01). There wasa significant inverse correlation between histological gradingand immunoreactivity for Bcl-2 (p < 0.001). No tumors tendedto be Bcl-2 positive, but differences were not statisticallysignificant. CONCLUSION:: Bcl-2 was detected predominantly in differentiated tumors. Expressionwas associated with other favorable histopathological featuresand predictors of positive clinical outcome. Loss of Bcl-2 expressionseems to be linked to loss of hormonal regulatability, increaseddifferentiation and deregulated proliferation. Bcl-2, breast cancer, immunohistochemistry, prognostic factors