Metilación de TP73 y upregulación de ΔNp73 correlacionan con agresividad tumoral en carcinoma de mama

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

Mendoza

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

The incidence of breast cancer is high inArgentina. The optimal treatment is based on proteomic and histologicalprognostic factors. We previously reported the correlation between aberrantmethylation of TP73 gene and high histological grade, one of the keypoor prognostic factors in invasive ductal breast carcinomas (IDC). The TP73protein has numerous isoforms with different biological and antagonisticfunctions. The goals of our study were to determine whether the TP73 genemethylation produces the silencing of TP73 and deltaN-p73 isoforms and tocorrelate TP73 methylation, silencing and expression with tumor aggressivenessand disease progression. For this, we evaluated the expression of TP73 isoformsin 42 IDC by immunohistochemistry and western blot. Previously, we have alsostudied in these tumors the TP73 gene methylation at two promoter regions byMLPA. Results showed a high expression of deltaN-p73 isoform in 69,7% of thesamples. Immunohistochemistry analysis revealed that all of the TP73 isoformswere localized in the nuclear compartment. No association was found betweenTP73 isoforms protein expression and the methylation status in the promoterregion of TP73 gene (p= 0.08). However, Fisher test and Spearman´s p confirmedthe association between delta-p73 expression with high histological grade (p=0.042) (p= 0,005). All together our data suggest that TP73 and deltaN-p73 areuseful factors to assess tumor aggressiveness in IDC.