E2F-1: A proliferative marker of breast neoplasia

E2F-1 is the best known ultimate transcription factor in the cyclin/cyclin- dependent kinase/retinoblastoma gene pathway and is probably involved in ca rcinogenesis and tumor progression. Because E2F-1 can be detected in paraff in sections using immunohistochemical techniques, it could be a useful tumo r/proliferation marker. We studied the expression of this gene product in 1 30 breast tissue specimens from 100 patients and compared it with the expre ssion of Mib-1, the widely used prognostic/proliferative marker, to assess E2F-1 as a new marker of neoplastic proliferation. The percentage of E2F-1- positive cells increased from 1.9% in the normal breast (NB) to 6.3% in duc tal carcinoma in situ (DCIS) and to 15.3% in invasive ductal carcinomas (ID C), In addition, higher-grade tumors as well as advanced-stage disease corr elated with higher expression of E2F-1, A similar tendency of Mib-1 express ion was observed. There was a positive correlation between the E2F-1 and Mi b-1 indices. In an in vitro experiment, me found that a similar difference in the expression of E2F-1 existed between a nontumorigenic breast cell lin e and two widely used breast carcinoma cell lines. The breast carcinoma cel l lines T-47D and MCF-7 had more E2F-1-positive cells than the nontumorigen ic cell line MCF-10F by immunohistochemistry and Western blot analysis. Bec ause E2F-1 expression was significantly higher in IDC and DCIS than in NB, this study indicates that deregulation of E2F-1 mag be involved in the deve lopment of breast IDC, In addition, E2F-1 expression could also be involved in tumor progression because the increased E2F-1 index correlated with the known prognostic predictors of breast cancer, such as histological grade, stage, metastasis status, estrogen receptor/progesterone receptor and Mib-1 expression. Thus, E2F-1 is a promising candidate to become a new prognosti c/predictive marker of breast cancer.