Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of "Copy-number Low" Tumors.

Autor:	Meljen VT, Mittenzwei R, Wong J, Puechl A, Whitaker R, Broadwater G, Hall AH, Bean SM, Bentley RC, Elvin JA, Berchuck A, Previs RA, Strickland KC
Jazyk:	angličtina
Zdroj:	International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists [Int J Gynecol Pathol] 2021 Nov 01; Vol. 40 (6), pp. 587-596.
DOI:	10.1097/PGP.0000000000000747
Abstrakt:	The study evaluated morphologic patterns, mutational profiles, and β-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n=19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides were reviewed. IHC for β-catenin was performed and correlated with mutation status. Images of digital slides of CNL EAs from The Cancer Genome Atlas (TCGA) database (n=90) were blindly reviewed by 4 pathologists, and morphology was correlated with mutation status. Categorical variables were analyzed using the Fisher exact test, and agreement was assessed using Fleiss κ. CTNNB1 mutations were present in 63% (12/19) of CNL EAs. β-catenin nuclear localization was present in 83% of CTNNB1-mutated tumors (10/12) and in 0% (0/7) of CTNNB1-wildtype tumors (sensitivity 0.83, specificity 1.00). Squamous differentiation (SD) was present in 47% (9/19) and was more often observed in CTNNB1-mutated tumors (P=0.02). Mucinous differentiation (MD) was associated with KRAS mutations (P<0.01). Digital image review of TCGA CNL EAs revealed that pathologist agreement on SD was strong (κ=0.82), whereas agreement on MD was weak (κ=0.48). Pathologists identified SD in 22% (20/90), which was significantly associated with the presence of CTNNB1 mutations (P<0.01). CNL EAs demonstrate several morphologies with divergent molecular profiles. SD was significantly associated with CTNNB1 mutations and nuclear localization of β-catenin in these tumors. Nuclear expression of β-catenin is a sensitive and specific IHC marker for CTNNB1 mutations in CNL EAs. CNL EAs with KRAS mutations often displayed MD. Competing Interests: K.C.S. is a consultant pathologist for Almac Pharmaceuticals and Foundation Medicine Inc. J.A.E. is Senior Vice President, Pathology and Diagnostic Medicine, for Foundation Medicine Inc. The remaining authors declare no conflict of interest. (Copyright © 2021 by the International Society of Gynecological Pathologists.)
Databáze:	MEDLINE
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