Clinicopathologic and Genomic Analysis of TP53-Mutated Endometrial Carcinomas

Abstract

Purpose: Copy number-high endometrial carcinomas (ECs) were described by The Cancer Genome Atlas as high-grade endometrioid and serous cancers showing frequent copy number alterations (CNAs), low mutational burden (i.e. non-hypermutant), near universal TP53 mutation and unfavorable clinical outcomes. We sought to investigate and compare the clinicopathologic and molecular characteristics of non-hypermutant TP53-altered ECs of four histologic types.Design: TP53-mutated ECs, defined as TP53-mutant tumors lacking microsatellite instability or pathogenic POLE mutations, were identified (n=238) in a cohort of 1,239 ECs subjected to clinical massively parallel sequencing of 410-468 cancer-related genes. Somatic mutations and CNAs

Performance of a HER2 testing algorithm specific for p53‐abnormal endometrial cancer

“…No difference was observed in the frequency of ERBB2 amplification between different histological subtypes. 12 These findings support the use of the molecular EC classification to direct HER2 testing in EC as opposed to histological subtype-directed HER2 testing. It is probably the most efficient approach to capture most, if not all, HER2positive EC.…”

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

“…The results indicate that using histologic subtype to attempt to “triage” cases to molecular subgroups may lead to significant problems with classification and suggest that markers should be applied independent of histology, this was also confirmed in the resent publication by Weigelt et al[25]. Applying TP53 immunohistochemistry on all cases of endometrioid FIGO 1 and 2 would represent a significant change for most pathology labs[26]. In our cohort, fully one-third (26/80, 33%) of P53abn cases would have been missed if endometrioid grade 1 and 2 cases were not stained.…”

Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

“…The results indicate that using histologic subtype to attempt to "triage" cases to molecular subgroups may lead to significant problems with classification and suggest that markers should be applied independent of histology, which was also confirmed in the resent publication by Weigelt et al [25]. Applying TP53 immunohistochemistry on all cases of endometrioid FIGO 1 and 2 would represent a significant change for most pathology labs [26]. In our cohort, fully one-third (26/80, 33%) of P53abn cases would have been missed if endometrioid grade 1 and 2 cases were not stained.…”