Abstract A15: Immunohistochemical patterns of the breast developmental gene, ELF5, reveals differential expression in high grade hormone receptor negative clinical breast cancer

ELF5 is a master regulator of breast lobular development, is enriched in luminal progenitor cells and has been implicated in breast carcinogenesis and may be a chemopreventive biomarker and target. In our laboratory, mammary cancer prone mice treated with the chemopreventive and anti-estrogen tamoxifen have fewer mammary hyperplastic lobules, reduced ELF5 mRNA expression and reduced tumor incidence. ELF5 mRNA is also expressed in multiple breast cancer cell lines and in clinical breast tumors of predominantly basal phenotype. However, the presence of ELF5 in cancer cells is not strictly a negative factor, as forced expression of ELF5 reduced aggressive phenotype in breast cancer cells and lung metastasis in mice with mammary tumors. In addition, in the clinics patients with tumors expressing higher levels of ELF5 mRNA had better outcomes than patients with tumors expressing lower levels. Taken together these data suggest ELF5 as a potential breast cancer biomarker worthy of further clinical assessment. In order to identify the cells that express ELF5 as well as to promote the routine assessment of ELF5 in clinical pathology laboratories, it would be highly advantageous to replace mRNA analysis with immunohistochemical analysis of ELF5. We therefore evaluated clinical cancer specimens for ELF5 protein expression patterns and compared outcomes to those published using ELF5 mRNA. We evaluated 106 formalin fixed and paraffin embedded breast tumors for the presence of ELF5 protein and intensity of antibody staining. In addition, we correlated ELF5 expression pattern with clinical and pathological features of tumors and patients. We found that ELF5 was highly expressed in stromal cells of all tumors but epithelial expression of ELF5 was limited to tumors of ductal origin including ductal carcinoma in situ and invasive carcinomas. We also found that a significantly higher proportion of tumors that were estrogen receptor negative (ER-) and/or progesterone receptor (negative PR-) were more likely to express epithelial ELF5 compared with ER + and/or PR+ tumors. In addition, tumor epithelial cell ELF5 expression was independent of HER2 status. Finally, epithelial ELF5 expression was significantly more frequent in higher grade tumors than in lower grade tumors. In conclusion, our ELF5 breast tumor immunohistochemistry results concur with studies using ELF5 tumor mRNA expression in that high grade tumors of ductal origin that are devoid of ER and/or PR are more likely to express ELF5. Taken together, these data indicate that ELF5 may provide unique prognostic information leading to segregation of patients with high grade tumors. Importantly, future evaluations of the clinical utility of ELF5 as a breast cancer biomarker can be carried out using standard pathology laboratory methods of immunohistochemistry. Citation Format: Donald Kundel, Melanie Bomier, Evan Odean, Olga Zhdankin, Mingqian Duan, Ronald Regal, Teresa Rose-Hellekant. Immunohistochemical patterns of the breast developmental gene, ELF5, reveals differential expression in high grade hormone receptor negative clinical breast cancer [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A15.