Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma

The phosphoinositide-3-kinase (PI3K) signaling pathway has been implicated in the development of endometrioid endometrial adenocarcinoma (EEC). Recently, The Cancer Genome Atlas (TCGA) project stratified EEC into four molecular subgroups, with the majority of tumors falling into the copy-number low-...

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Main Author:	LIN, DOUGLAS I.
Format:	Online
Language:	English
Published:	D.A. Spandidos 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665731/

id	pubmed-4665731
recordtype	oai_dc
spelling	pubmed-46657312015-12-31 Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma LIN, DOUGLAS I. Articles The phosphoinositide-3-kinase (PI3K) signaling pathway has been implicated in the development of endometrioid endometrial adenocarcinoma (EEC). Recently, The Cancer Genome Atlas (TCGA) project stratified EEC into four molecular subgroups, with the majority of tumors falling into the copy-number low-EEC (CNL-EEC) molecular subgroup. The aim of the present study was to investigate whether alterations of the PI3K pathway are associated with specific survival outcomes in patients with EEC. The clinical and genomic data of 307 patients with endometrioid-type tumors were obtained from TCGA project, including 90 patients in the CNL-EEC subgroup. Patients were evaluated in terms of survival and clinicopathological characteristics, as well as mutations in the PI3K catalytic subunit alpha (PIK3CA) gene and their effect on PIK3CA function. In CNL-EEC subgroup patients, somatic PIK3CA mutations (48/90 cases) were associated with significantly improved overall survival compared with that of wild-type PIK3CA (P=0.018). Furthermore, this improved survival was specific to the CNL-EEC subgroup and was not observed in other TCGA molecular subgroups. The majority of CNL-EEC cases were low-stage (stage I) and low-to-intermediate grade (grades 1–2) endometrioid tumors. There were no significant differences in age, stage, histology or International Federation of Gynecology and Obstetrics grade between PIK3CA-mutated and non-mutated patient groups (P>0.05). In addition, the majority of cases contained activating PIK3CA mutations. Overall, in the TCGA cohort, PIK3CA mutations had a favorable effect on the survival of patients with EEC, and this effect was dependent on tumoral molecular sub-stratification. Future studies on larger independent cohorts with long term follow-up are warranted to further analyze this association. D.A. Spandidos 2015-11 2015-09-15 /pmc/articles/PMC4665731/ /pubmed/26722235 http://dx.doi.org/10.3892/ol.2015.3702 Text en Copyright: © Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	LIN, DOUGLAS I.
spellingShingle	LIN, DOUGLAS I. Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma
author_facet	LIN, DOUGLAS I.
author_sort	LIN, DOUGLAS I.
title	Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma
title_short	Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma
title_full	Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma
title_fullStr	Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma
title_full_unstemmed	Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma
title_sort	improved survival associated with somatic pik3ca mutations in copy-number low endometrioid endometrial adenocarcinoma
description	The phosphoinositide-3-kinase (PI3K) signaling pathway has been implicated in the development of endometrioid endometrial adenocarcinoma (EEC). Recently, The Cancer Genome Atlas (TCGA) project stratified EEC into four molecular subgroups, with the majority of tumors falling into the copy-number low-EEC (CNL-EEC) molecular subgroup. The aim of the present study was to investigate whether alterations of the PI3K pathway are associated with specific survival outcomes in patients with EEC. The clinical and genomic data of 307 patients with endometrioid-type tumors were obtained from TCGA project, including 90 patients in the CNL-EEC subgroup. Patients were evaluated in terms of survival and clinicopathological characteristics, as well as mutations in the PI3K catalytic subunit alpha (PIK3CA) gene and their effect on PIK3CA function. In CNL-EEC subgroup patients, somatic PIK3CA mutations (48/90 cases) were associated with significantly improved overall survival compared with that of wild-type PIK3CA (P=0.018). Furthermore, this improved survival was specific to the CNL-EEC subgroup and was not observed in other TCGA molecular subgroups. The majority of CNL-EEC cases were low-stage (stage I) and low-to-intermediate grade (grades 1–2) endometrioid tumors. There were no significant differences in age, stage, histology or International Federation of Gynecology and Obstetrics grade between PIK3CA-mutated and non-mutated patient groups (P>0.05). In addition, the majority of cases contained activating PIK3CA mutations. Overall, in the TCGA cohort, PIK3CA mutations had a favorable effect on the survival of patients with EEC, and this effect was dependent on tumoral molecular sub-stratification. Future studies on larger independent cohorts with long term follow-up are warranted to further analyze this association.
publisher	D.A. Spandidos
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665731/
_version_	1613508264431976448

Improved survival associated with somatic PIK3CA mutations in copy-number low endometrioid endometrial adenocarcinoma

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