Abstract 4786: Cellular localization of PRMT5 correlates with poor recurrent free survival in triple-negative breast cancer (TNBC)

PURPOSE: TNBC is an aggressive disease with limited effective targeted therapies. Protein arginine methyltransferase 5 (PRMT5) is an enzyme that symmetrically methylates arginine residues of both histone and non-histone proteins that regulate cellular growth and drive malignant transformation. PRMT5 is an oncogenic marker for aggressive cancers with limited treatment options like glioblastoma multiforme (GBM) and mantle cell lymphoma (MCL) and PRMT5 knockdown has been shown to improve survival in a preclinical model of GBM. The expression profile of PRMT5 in TNBC has not been previously evaluated. METHODS: We obtained a clinical database of TNBC patients that correlates to tissue samples collected after resection of the original breast tumor (n = 106). Tissue microarrays (TMA) were stained for PRMT5 and graded based on level of cytoplasmic and nuclear staining. The association of PRMT5 expression with patient overall survival (OS) and recurrent free survival (RFS) was analyzed using a log-rank test. Multivariate COX regression model was used to evaluate PRMT expression level as independent predictor of OS and RFS with histopathologic factors such as lymph node involvement and tumor size. RESULTS: High cytoplasmic levels of PRMT5 in TNBC correlated with improvement in RFS (p = 0.043, CI 0.218-0.976), while showing no correlation with OS. High levels of nuclear PRTM5 did not show a significant correlation with OS or RFS. Patients with tumors showing high nuclear and low cytoplasmic levels of PRMT5 had the worst OS and RFS (p