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Validated biomarker assays confirm that <scp>ARID1A</scp> loss is confounded with <scp>MMR</scp> deficiency, <scp> CD8 + TIL </scp> infiltration, and provides no independent prognostic value in endometriosis‐associated ovarian carcinomas

Authors :
Karolin Heinze
Tayyebeh M Nazeran
Sandra Lee
Pauline Krämer
Evan S Cairns
Derek S Chiu
Samuel CY Leung
Eun Young Kang
Nicola S Meagher
Catherine J Kennedy
Jessica Boros
Friedrich Kommoss
Hans‐Walter Vollert
Florian Heitz
Andreas Bois
Philipp Harter
Marcel Grube
Bernhard Kraemer
Annette Staebler
Felix KF Kommoss
Sabine Heublein
Hans‐Peter Sinn
Naveena Singh
Angela Laslavic
Esther Elishaev
Alex Olawaiye
Kirsten Moysich
Francesmary Modugno
Raghwa Sharma
Alison H Brand
Paul R Harnett
Anna DeFazio
Renée T Fortner
Jan Lubinski
Marcin Lener
Aleksandra Tołoczko‐Grabarek
Cezary Cybulski
Helena Gronwald
Jacek Gronwald
Penny Coulson
Mona A El‐Bahrawy
Michael E Jones
Minouk J Schoemaker
Anthony J Swerdlow
Kylie L Gorringe
Ian Campbell
Linda Cook
Simon A Gayther
Michael E Carney
Yurii B Shvetsov
Brenda Y Hernandez
Lynne R Wilkens
Marc T Goodman
Constantina Mateoiu
Anna Linder
Karin Sundfeldt
Linda E Kelemen
Aleksandra Gentry‐Maharaj
Martin Widschwendter
Usha Menon
Kelly L Bolton
Jennifer Alsop
Mitul Shah
Mercedes Jimenez‐Linan
Paul DP Pharoah
James D Brenton
Kara L Cushing‐Haugen
Holly R Harris
Jennifer A Doherty
Blake Gilks
Prafull Ghatage
David G Huntsman
Gregg S Nelson
Anna V Tinker
Cheng‐Han Lee
Ellen L Goode
Brad H Nelson
Susan J Ramus
Stefan Kommoss
Aline Talhouk
Martin Köbel
Michael S Anglesio
Source :
J Pathol
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p

Details

ISSN :
10969896 and 00223417
Volume :
256
Database :
OpenAIRE
Journal :
The Journal of Pathology
Accession number :
edsair.doi.dedup.....ef7ba5778ffc8717d03a4c6c54165fc9