TP73 methylation and upregulation of deltaNP73 correlate with breast carcinoma aggressiveness

GOMEZ LC; SOTTILE ML; GAGO FE; OROZCO JI; MARZESE DM; ROQUÉ MORENO M.; NADIN SB; VARGAS ROIG LM

Mendoza

Congreso; XXXIV Reunión Científica Anual de la Sociedad de Biología de Cuyo.; 2016

The incidence of breast cancer is high in Argentina. The optimal treatment is based on proteomic and histological prognostic factors. We previously reported the correlation between aberrant methylation of TP73 gene and high histological grade, one of the key poor prognostic factors in invasive ductal breast carcinomas (IDC). The TP73 protein has numerous isoforms with different biological and antagonistic functions. The goals of our study were to determine whether the TP73 gene methylation produces the silencing of TP73 and ΔN-p73 isoforms and to correlate TP73 methylation, silencing and expression with tumor aggressiveness and disease progression. For this, we evaluated the expression of TP73 isoforms in 42 IDC by immunohistochemistry and western blot. Previously, we have also studied in these tumors the TP73 gene methylation at two promotor regions by MLPA. Results showed a high expression of ΔN-p73 isoform in 69,7% of the samples. Immunohistochemistry analysis revealed that all of the TP73 isoforms were localized in the nuclear compartment. No association was found between TP73 isoforms protein expression and the methylation status in the promotor region of TP73 gene (p= 0.08). However, Fisher test and Sperarman´s p confirmed the association between ΔN-p73 expression with high histological grade (p= 0.042), (p= 0,005). All together our data suggest that TP73 and ΔN-p73 are useful factors to assess tumor aggressiveness in IDC.