TY - JOUR
T1 - β-catenin, Pax2, and Pten Panel Identifies Precancers among Histologically Subdiagnostic Endometrial Lesions
AU - Aguilar, Mitzi
AU - Chen, Hao
AU - Sahoo, Subhransu S.
AU - Zheng, Wenxin
AU - Grubman, Jessica
AU - Sorelle, Jeffrey A.
AU - Lucas, Elena
AU - Castrillon, Diego H.
N1 - Funding Information:
The authors gratefully acknowledge support from the Mary Kay Ash Foundation (09-22), the Vernie A. Stembridge Fund, and the UTSW Tissue Management Facility through the UTSW Simmons Comprehensive Cancer Center Support Grant P30 CA142543.
Publisher Copyright:
© Copyright 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Despite refinements in histologic criteria for the diagnosis of endometrioid precancers, many challenging cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of β-catenin, Pax2, and Pten was identified as a useful diagnostic adjunct. However, previous studies focused either on cancers or diagnostically unambiguous precancers, leaving questions about the applicability and utility of the panel in endometria with architectural features near or below the threshold of accepted histologic criteria for endometrioid precancers. Here, in a retrospective study of 90 patients, we evaluated the performance of the 3-marker panel. Notably, the panel detected a subset of disordered proliferative endometria (8/44, 18%), nonatypical hyperplasias (19/40, 48%), and cases with ambiguous features (3/6, 50%) with aberrancy for ≥1 markers. Marker-aberrant cases were more likely to progress to endometrioid precancer or cancer (P=0.0002). Patterns of marker aberrancy in the index and progressor cases from individual patients provided evidence for origin in a common precursor, and next-generation sequencing of the progressor cases rationalized marker aberrancy for β-catenin and Pten. The results unequivocally demonstrate that some lesions that do not approach current histologic thresholds are bona fide neoplastic precursors with clinically-relevant driver events that can be detected by the 3-marker panel. The findings provide further validation for the diagnostic utility of the panel in clinical practice and its application in difficult or ambiguous cases.
AB - Despite refinements in histologic criteria for the diagnosis of endometrioid precancers, many challenging cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of β-catenin, Pax2, and Pten was identified as a useful diagnostic adjunct. However, previous studies focused either on cancers or diagnostically unambiguous precancers, leaving questions about the applicability and utility of the panel in endometria with architectural features near or below the threshold of accepted histologic criteria for endometrioid precancers. Here, in a retrospective study of 90 patients, we evaluated the performance of the 3-marker panel. Notably, the panel detected a subset of disordered proliferative endometria (8/44, 18%), nonatypical hyperplasias (19/40, 48%), and cases with ambiguous features (3/6, 50%) with aberrancy for ≥1 markers. Marker-aberrant cases were more likely to progress to endometrioid precancer or cancer (P=0.0002). Patterns of marker aberrancy in the index and progressor cases from individual patients provided evidence for origin in a common precursor, and next-generation sequencing of the progressor cases rationalized marker aberrancy for β-catenin and Pten. The results unequivocally demonstrate that some lesions that do not approach current histologic thresholds are bona fide neoplastic precursors with clinically-relevant driver events that can be detected by the 3-marker panel. The findings provide further validation for the diagnostic utility of the panel in clinical practice and its application in difficult or ambiguous cases.
KW - Arid1a
KW - Mlh1
KW - Pax2
KW - Pten
KW - atypical hyperplasia
KW - biomarkers
KW - endometrial cancer
KW - endometrial precancer
KW - endometrioid intraepithelial neoplasia
KW - β-catenin
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U2 - 10.1097/PAS.0000000000002034
DO - 10.1097/PAS.0000000000002034
M3 - Article
C2 - 36939046
AN - SCOPUS:85152631206
SN - 0147-5185
VL - 47
SP - 618
EP - 629
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 5
ER -