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

<h4>Objective</h4>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).<h4>Methods</h4>Direct sequencing of POLE exonuclease domain hot spots and im...

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Autores principales:	Annukka Pasanen, Mikko Loukovaara, Terhi Ahvenainen, Pia Vahteristo, Ralf Bützow
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d71ddb2b73cd4825865a760f909702f2
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spelling	oai:doaj.org-article:d71ddb2b73cd4825865a760f909702f22021-12-02T20:08:38ZDifferential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.1932-620310.1371/journal.pone.0253472https://doaj.org/article/d71ddb2b73cd4825865a760f909702f22021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253472https://doaj.org/toc/1932-6203<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.Annukka PasanenMikko LoukovaaraTerhi AhvenainenPia VahteristoRalf BützowPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0253472 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Annukka Pasanen Mikko Loukovaara Terhi Ahvenainen Pia Vahteristo Ralf Bützow Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.
description	<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
format	article
author	Annukka Pasanen Mikko Loukovaara Terhi Ahvenainen Pia Vahteristo Ralf Bützow
author_facet	Annukka Pasanen Mikko Loukovaara Terhi Ahvenainen Pia Vahteristo Ralf Bützow
author_sort	Annukka Pasanen
title	Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.
title_short	Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.
title_full	Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.
title_fullStr	Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.
title_full_unstemmed	Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.
title_sort	differential impact of clinicopathological risk factors within the 2 largest promise molecular subgroups of endometrial carcinoma.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d71ddb2b73cd4825865a760f909702f2
work_keys_str_mv	AT annukkapasanen differentialimpactofclinicopathologicalriskfactorswithinthe2largestpromisemolecularsubgroupsofendometrialcarcinoma AT mikkoloukovaara differentialimpactofclinicopathologicalriskfactorswithinthe2largestpromisemolecularsubgroupsofendometrialcarcinoma AT terhiahvenainen differentialimpactofclinicopathologicalriskfactorswithinthe2largestpromisemolecularsubgroupsofendometrialcarcinoma AT piavahteristo differentialimpactofclinicopathologicalriskfactorswithinthe2largestpromisemolecularsubgroupsofendometrialcarcinoma AT ralfbutzow differentialimpactofclinicopathologicalriskfactorswithinthe2largestpromisemolecularsubgroupsofendometrialcarcinoma
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Differential impact of clinicopathological risk factors within the 2 largest ProMisE molecular subgroups of endometrial carcinoma.

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