Expression and subcellular localization of P73 as prognosis in breast cancer subtypes

GOMEZ LC; SOTTILE ML; REDONDO AL; MARZESE DM; VARGAS ROIG LM

San Luis

Congreso; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2019

Sociedad de Biología de Cuyo

The incidence of breast cancer (BC) is high in Argentina. The optimal treatment is based on proteomic and histological prognostic factors. Based on variations in gene expression, BC patients are currently classified into five major subtypes: luminal A, luminal B, ErbB2+, basal-like and normal-like. We previously reported that the methylation of TP73 differed significantly between molecular subtypes. Luminal A tumours frequently exhibited unmethylated TP73; in contrast, all basal-like tumours exhibited methylated TP73.The P73 protein has numerous isoforms with different biological and antagonistic functions. The goals of our study were to determine the expression and subcellular localization of the P73 isoforms, its relationship with TP73 methylation and their clinical prognostic significance in BC subtypes. For this, we evaluated the expression and subcellular localization of TA-p73 and ΔNp73 isoforms in 137 invasive breast tumors and 3 BC cell lines by immunohistochemistry and immunofluorescence, respectively. The results showed an exclusive nuclear localization of TA-p73 isoform in 88.9% of luminal BC tumors expressing this isoform. In contrast, basal-like and ErbB2+ tumors mainly exhibited cytoplasmatic expression of TA-p73 isoform in 69,9% and 72%, respectively. The ΔNp73 isoform was mainly expressed in cytoplasm of all breast tumors with different molecular subtypes. Concomitant, TA-p73 isoform was localized almost exclusively at the nucleus of luminal BC cell lines, while it was mainly expressed in cytoplasm of basal-like cell line. All together our data suggest that expression and subcellular localization of p73 isoforms are useful factors as prognosis in breast cancer subtypes.