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 carcinogenesis and tumor progression. Because E2F-1 can be detected in paraffin sections using immunohistochemical techniques, it could be a useful tumor/proliferation marker. We studied the expression of this gene product in 130 breast tissue specimens from 100 patients and compared it with the expression 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 ductal carcinoma in situ (DCIS) and to 15.3% in invasive ductal carcinomas (IDC). In addition, higher-grade tumors as well as advanced-stage disease correlated with higher expression of E2F-1. A similar tendency of Mib-1 expression was observed. There was a positive correlation between the E2F-1 and Mib-1 indices. In an in vitro experiment, we found that a similar difference in the expression of E2F-1 existed between a nontumorigenic breast cell line and two widely used breast carcinoma cell lines. The breast carcinoma cell lines T-47D and MCF-7 had more E2F-1-positive cells than the nontumorigenic cell line MCF-10F by immunohistochemistry and Western blot analysis. Because E2F-1 expression was significantly higher in IDC and DCIS than in NB, this study indicates that deregulation of E2F-1 may be involved in the development 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 prognostic/predictive marker of breast cancer.
Zhang
S Y
SY
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Liu
S C
SC
Al-Saleem
L F
LF
Holloran
D
D
Babb
J
J
Guo
X
X
Klein-Szanto
A J
AJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors