Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative

Gynecologic Oncology
Richard J EdmondsonH C Kitchener

Abstract

The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63. About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. O...Continue Reading

Citations

Sep 26, 2017·Advances in Anatomic Pathology·Oluwole FadareVighnesh Walavalkar
Oct 12, 2018·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·Frédéric AmantCarien L Creutzberg
Dec 15, 2018·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Joseph T RabbanW Glenn McCluggage
Mar 10, 2020·Journal of Cellular and Molecular Medicine·Qian WangJianchao Ying
Nov 7, 2019·International Journal of Molecular Sciences·Mitsuhiro NakamuraHiroshi Fujiwara
Aug 28, 2020·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Alyssa LarishAndrea Mariani

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