Abstract 803P
Background
Endometrial cancers (EC) mutated in the exonuclease domain of the polymerase epsilon gene (POLE mut) accounts for 8-10% of EC and have an excellent outcome. POLE sequencing is not routinely performed but emerging guidelines suggest that POLE mut stage I–II EC may spare adjuvant treatment while advanced POLE mut EC are eligible for a check point inhibitor. Given its therapeutic impact, we aimed at identifying surrogate pathological markers suggesting POLE mut.
Methods
140 consecutive EC diagnosed between 2010 and 2019 were sequenced. POLE variants affecting exonuclease domain were characterized by next-generation sequencing (NGS) based on formalin-fixed paraffin-embedded (FFPE) tissues. Only well described hotspot mutations were considered. We assessed morphological characteristics including histological subtype, grade, mitotic index and tumor-infiltrating lymphocytes (moderate to dense infiltrate), and evaluated their diagnostic properties to detect POLE mutations.
Results
Somatic hotspot POLE mutations were identified in 13 (9.3%) tumors while 6 (4.3%) had variants of unknown significance (VSI). POLE mut (without VSI) and wt tumors were similar regarding endometrioid subtype (92.3% vs 82.8%, p=X), grade (18.2% vs 27.1% of high grade, p=X) and presence of embols (7.7% vs 11.5%, p=X) respectively. Mean of mitotic index was also similar: 6.1 (5.3) mitoses/mm2 vs 7.7 (7.4). The presence of TILS was similar in POLE mut and wt tumors: 61.5% vs 41.7% (p=X) respectively. Using TILS (moderate to dense infiltrate), low grade and endometrioid histology, sensitivities were 62%, 82% and 92% respectively, and negative predictive values were 94%, 94% and 95% respectively.
Conclusions
An histopathological algorithm with endometrioid tumor, high grade, TILs, doesn’t allow detect EC POLE mut. The molecular analysis will be soon necessary.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institut Cancerologie de l'Ouest.
Funding
Tesaro.
Disclosure
P. Augereau: Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker: Lilly; Financial Interests, Invited Speaker: Pfizer. J. Frenel: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: Novocure; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Principal Investigator: Novartis; Non-Financial Interests, Principal Investigator: Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Pfizer; Non-Financial Interests, Principal Investigator: Daiichi; Non-Financial Interests, Principal Investigator: MSD. All other authors have declared no conflicts of interest.