TP73 DNA methylation and Upregulation of deltaNp73 are associated with an adverse prognosis in breast cancer

GOMEZ LC; SOTTILE ML; GUERRERO-GIMENEZ ME; ZOPPINO FCM; REDONDO AL; GAGO FE; OROZCO JI; TELLO OM; ROQUÉ M.; NADIN SB; MARZESE DM; VARGAS ROIG LM

JOURNAL OF CLINICAL PATHOLOGY

B M J PUBLISHING GROUP

Lugar: Londres; Año: 2017

0021-9746

Aims Accumulated evidences support the fact that aberrantmethylation of TP73 gene andincreased levels of deltaNp73 in primary tumors have been shown to correlate withpoor prognosis. However, little is known regarding the transcriptional andfunctional regulation of the TP73gene in breast cancer. The aim of the present study was to determine theexpression of deltaNp73 isoform, its relation to DNA methylation of TP73 and their clinical prognosticsignificance in breast cancer patients. Methods The TP73 gene methylation was studied inTCGA datasets and in 70 invasive ductal breast carcinomas (IDC). The expression of p73 isoforms was evaluated byimmunohistochemistry and western blot and it was correlated with clinicopathological variables and clinical outcome. Results We observed that the methylation of diverse CpG islands of TP73differed significantly between molecular subtypes. Inverse correlation wasfound between p73 protein expression and the methylation status of TP73 gene. The expression of exon 3?of p73 (only expressed in ΔNp73), wassignificantly higher in patients with wild-type p53. Immunohistochemistryanalysis revealed that all p73 isoforms were localized in both the nuclear andcitoplasmatic compartment. We confirmed towards a positive association betweenexpression of deltaNp73 and high histological grade. Conclusions Our findings suggest that high expression of deltaNp73 could be could be used to determine the aggressiveness of IDCs and could beincorporated in the pathologist´s report.