Expression and subcellular localization of p73 as prognosis in breast cancer subtypes

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

San Luis

Congreso; XXXIVII Reunión Científica Anual de la SBCuyo; 2019

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 was to determine the expression and cellular localization of the P73 isoforms, its relationship with TP73 methylation and their clinical prognostic significance in breast cancer subtypes. For this, we evaluated the expression and cellular localization of TA-p73 and ΔNp73 isoforms in 137 breast tumors and breast cells lines by immunohistochemistry (IHC) and immunofluorescence. Results showed a TA-p73 isoform localized exclusively to the nucleus in 88,9% of cells in which it was expressed in luminal tumors, with only weak cytoplasmic staining. In contrast, basal -like and ErbB2+ tumors mainly exhibit cytoplasmatyc expression of TA-p73 isoform in 69,9% and 72% respectively. Concomitant, TA-p73 isoform was localized almost exclusively at the nucleus of luminal cell lines, while in basal like cell line was mainly expressed in cytoplasm. Association analysis revealed that most luminal A tumours exhibited unmethylated TP73 (p=0.004). In contrast, all triple negative tumours exhibited methylated TP73 (p