Objectives The molecular classification of endometrial carcinoma (EC) is taking the diagnosis on EC to a more comprehensive level and will aid to better identify those patients whose disease is likely to behave differently than predicted when using traditional risk stratification. We are transitioning towards the use of molecular classification in a clinical context; however, it remains undetermined, which would be the optimal approach.
Methods In this study,s we characterized patients (n=60) whose disease had a different than anticipated clinical course determined by current risk stratification tools and histomorphologically corresponding control samples. The aim was to access the molecular classification using two different methods; by performing the FoundationOne CDx NGS panel and using the ProMisE classifier and performing immunohistochemical stainings for MMR proteins and p53. POLE mutation status was in both settings derived from FoundationOne results.
Results 64 patients were entered in this study, and in 60 cases, the molecular classification was successful. MSI status was available from 53 cases. Tumour molecular subtype was of prognostic significance and showed the expected correlations with grade and histotype. Molecular subtype diagnosis based on NGS and ProMisE was in complete agreement for 50 of 53 tumors. In 2 tumors, a TP53 mutation was detected on NGS, but immunostaining showed subclonal pattern, and 1 case was MSI based on NGS but MMR deficient by immunohistochemistry.
Conclusions Both NGS panel sequencing of formalin-fixed paraffin embedded endometrial carcinomas and molecular subtype diagnosis based primarily on immunostaining (ProMisE) yield identical results in 94.3% (kappa – 0.91) of cases.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.