TP73 DNA methylation and upregulation of ΔNp73 are associated with an adverse prognosis in breast cancer

GOMEZ, LAURA C; SOTTILE, MAYRA L; GUERRERO-GIMENEZ, MARTIN E; ZOPPINO, FELIPE C M; REDONDO, ANALIA L; GAGO, FRANCISCO E; OROZCO, JAVIER I; TELLO, OLGA M; ROQUÉ, MARIA; NADIN, SILVINA B; MARZESE, DIEGO M; VARGAS-ROIG, LAURA M

JOURNAL OF CLINICAL PATHOLOGY

B M J PUBLISHING GROUP

Año: 2018 vol. 71 p. 52 - 58

0021-9746

Aim Accumulated evidence suggests that aberrantmethylation of the TP73 gene and increased levels ofΔNp73 in primary tumours correlate with poor prognosis.However, little is known regarding the transcriptional andfunctional regulation of the TP73 gene in breast cancer.The aim of the present study was to determine theexpression of the ΔNp73 isoform, its relationship withDNA methylation of TP73 and their clinical prognosticsignificance in breast cancer patients.Methods TP73 gene methylation was studied in TCGAdatasets and in 70 invasive ductal breast carcinomas(IDCs). The expression of p73 isoforms was evaluatedby immunohistochemistry (IHC) and Western blot andcorrelated with clinicopathological variables and clinicaloutcome.Results We observed that the methylation of diverseCpG islands of TP73 differed significantly betweenmolecular subtypes. An inverse correlation was foundbetween p73 protein expression and the methylationstatus of the TP73 gene. The expression of exon 3? ofp73 (only expressed in ΔNp73) was significantly higherin patients with wild-type p53. Immunohistochemicalanalysis revealed that all p73 isoforms were localisedin both the nuclear and cytoplasmic compartments. Weconfirmed a positive association between the expressionof ΔNp73 and high histological grade.Conclusions Our findings suggest that highexpression of ΔNp73 could be used to determine theaggressiveness of IDCs and could be incorporated in thepathologist?s report.