730 Analysis of EMSY in Italian Male Breast Cancer Patients

Background: Male breast cancer (MBC) is a rare disease compared to female breast cancer (FBC). MBC shares many similarities with FBC, including genetic predisposition factors such as BRCA1/2, CHEK2, PALB2, BRIP1 and RAD51C mutations. However, these alterations can explain only 10% of MBC cases, thus suggesting the contribution of additional susceptibility genes. EMSY has been recently identified as a gene involved in FBC pathogenesis because EMSY can interact with BRCA2 and in this way it is capable of silencing the activation potential of BRCA2. Moreover, breast tumors with amplified EMSY show a phenotypic profile that is similar to BRCA2-related tumors. So, because of the interaction between BRCA2 and EMSY, the latter could play a relevant role in MBC and could explain those MBC cases which pathogenesis can’t be related to BRCA1/BRCA2 mutations. To date, there are no information about the role of EMSY in the pathogenesis of MBC. Taking into account that EMSY has a prognostic value for FBC, studies on its role could have important implications in the elucidation of pathogenetic mechanisms of MBC and in the clinical management of MBC patients. Material and Methods: This study was performed on a series of 100 MBC cases characterized for BRCA1/BRCA2 germ-line mutations and for relevant clinicopathologic features. We have investigated the presence of germ-line mutations and amplification of EMSY by automatic sequencing and qRT-PCR respectively. Statistical analysis was performed using the Fisher exact test. Results: We have found EMSY alterations in 5% of our series. Three of the 37 variants identified (M83K, M1197I and IVS5−1G>A) were shown to be probably damaging by using two prediction softwares. We have found a general amplification percentage of 44% and we have distinguished three different amplification subgroups. A statistically significant association emerged between EMSY amplification and MIB1 (p = 0.03) expression. Conclusions: Our data indicate that alterations of EMSY are involved in MBC pathogenesis at a comparable level as in FBC. New coding variants of this gene seems to be involved in MBC pathogenesis and EMSY amplification allows the identification of distinct subgroups of MBC cases. Moreover, although larger studies are needed, our results suggest that EMSY could be involved not only in MBC pathogenesis but also in tumor progression. Study supported by AIRC (IG 8713).