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

LAURA C GOMEZ; MAYRA L SOTTILE FLEURY; MARTÍN E GUERRERO-GIMENEZ; FELIPE CM ZOPPINO; ANALIA REDONDO; FRANCISCO E GAGO; JAVIER I OROZCO; OLGA M TELLO; MARÍA ROQUÉ; SILVINA B NADIN; DIEGO M. MARZESE; LAURA M VARGAS-ROIG

JOURNAL OF CLINICAL PATHOLOGY

B M J PUBLISHING GROUP

Lugar: Londres; Año: 2017 vol. 71 p. 52 - 58

0021-9746

Aim Accumulated evidence supports the fact that aberrant methylation of TP73 gene and increased levels of ΔNp73 in primary tumors have been shown to correlate with poor prognosis. However, little is known regarding the transcriptional and functional regulation of the TP73 gene in breast cancer. The aim of the present study was to determine the expression of ΔNp73 isoform, its relation to DNA methylation of TP73 and their clinical prognostic significance in breast cancer patients.Methods The TP73 gene methylation was studied in TCGA datasets and in 70 invasive ductal breast carcinomas (IDC). The expression of p73 isoforms was evaluated by immunohistochemistry and western blot and it was correlated with clinicopathological variables and clinical outcome.Results We observed that the methylation of diverse CpG islands of TP73 differed significantly between molecular subtypes. Inverse correlation was found between p73 protein expression and the methylation status of TP73 gene. The expression of exon 3?of p73 (only expressed in ΔNp73), was significantly higher in patients with wild-type p53. Immunohistochemistry analysis revealed that all p73 isoforms were localized in both the nuclear and cytoplasmic compartment. We confirmed towards a positive association between expression of ∆Np73 and high histological grade. Conclusions Our findings suggest that high expression of ΔNp73 could be used to determine the aggressiveness of IDCs and could be incorporated in the pathologist´s report.