Interferon regulatory factor expression in human breast cancer

Objective To investigate the expression of interferon regulatory factors 1 and 2 (IRF-1 and IRF-2) in human breast cancer. Summary Background Data Interferon regulatory factors 1 and 2 are transcrip tion factors in the interferon gamma signal transduction pathway. IRF-1 act s as the effector arm of the interferon gamma response; IRF-2 binds to the same DNA consensus sequence and opposes IRF-1 activity. Previous work in th e authors' laboratory has shown the tumor suppressor activity of IRF-1 expr ession and the oncogenic effect of IRF-2 in human and murine tumor models, including human breast cancer cell lines. The authors' hypothesis is that t his pathway is involved in human tumor development. and alterations in the expression of IRF-1 and IRF-2 may occur in breast cancer tissue compared wi th normal breast tissue, and between more and less differentiated breast ca ncers. Methods Formalin-fixed paraffin-embedded human archival tissue specimens we re obtained from 33 patients with pure ductal carcinoma in situ (DCIS) and 49 women with invasive ductal cancer. Adjacent areas of normal breast tissu e were assayed in 31 women. These specimens were stained with polyclonal IR F-1 and IRF-2 antibodies using an avidin-biotin-peroxidase complex techniqu e after epitope retrieval. Results Most normal breast tissue showed expression of IRF-1 and no express ion of IRF-2 by immunohistochemistry. High-grade DCIS or node-positive inva sive ductal cancers were less likely to express the tumor suppressor IRF-1 than normal tissue. More strikingly, high-grade DCIS and invasive ductal ca ncers were much more likely to express the oncogenic IRF-2 protein than was normal tissue. Conclusions Expression of IRF-1 and IRF-2 is altered in human breast cancer compared with normal adjacent tissue. The loss of IRF-1 expression is cons istent with tumor suppressor loss and the development of IRF-2 expression w ith oncogenic activation. These data support the hypothesis that this pathw ay is involved in human breast oncogenesis, which warrants further investig ation regarding prognostic and therapeutic implications.