Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma

Show full item record



Permalink

http://hdl.handle.net/10138/336885

Citation

Pasanen , A , Loukovaara , M , Ahvenainen , T , Vahteristo , P & Bützow , R 2021 , ' Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma ' , PLoS One , vol. 16 , no. 9 , 0253472 . https://doi.org/10.1371/journal.pone.0253472

Title: Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma
Author: Pasanen, Annukka; Loukovaara, Mikko; Ahvenainen, Terhi; Vahteristo, Pia; Bützow, Ralf
Contributor organization: HUSLAB
Department of Pathology
Medicum
ATG - Applied Tumor Genomics
Clinicum
Department of Obstetrics and Gynecology
HUS Gynecology and Obstetrics
Department of Medical and Clinical Genetics
Date: 2021-09-02
Language: eng
Number of pages: 11
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0253472
URI: http://hdl.handle.net/10138/336885
Abstract: Objective To assess whether the prognostic impact of conventional risk factors and ancillary biomarkers differs across the 2 largest ProMisE molecular subgroups of endometrial carcinoma (EC). Methods Direct sequencing of POLE exonuclease domain hot spots and immunohistochemistry for MLH1, PMS2, MSH2, MSH6 and p53 were performed on 745 unselected endometrioid ECs to identify mismatch repair deficient (MMR-D, n = 264) and no specific molecular profile (NSMP, n = 206) ECs. Molecular group-specific survival analyses and interaction analyses were performed to determine the prognostic relevance of clinicopathological factors and various biomarkers (L1 cell adhesion molecule, estrogen and progesterone receptor, beta-catenin, p16, E-cadherin, KRAS) within the subgroups. Results Molecular subgroup did not have an independent effect on disease-specific survival after adjustment for conventional risk factors (P = 0.101). High grade (G3) and p16 hyperexpression remained significant predictors of survival in NSMP. Stage II-IV, >= 50% myometrial invasion, lymphovascular space invasion and loss of E-cadherin were independent predictors in the MMR-D group. In the interaction analysis, molecular subclass significantly modified the prognostic effect of high grade and p16 hyperexpression, which showed a stronger negative effect on survival in NSMP as compared to MMR-D (P for interaction = 0.016 for grade and 0.033 for p16). Conclusions Grade of differentiation and p16 hyperexpression appear to have a stronger prognostic impact in NSMP as compared to MMR-D EC. While these results need to be confirmed in a larger study population, they indicate that differential impact of risk factors needs to be taken into account when developing new molecular class-integrated risk stratification algorithms for EC.
Subject: TISSUE MICROARRAY TECHNOLOGY
CELL-ADHESION MOLECULE
CANCER
REPRODUCIBILITY
PREDICTOR
SURVIVAL
CLASSIFICATION
VALIDATION
DIAGNOSIS
L1CAM
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
journal.pone.0253472_1_.pdf 650.4Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record