β-catenin, Pax2, and Pten Panel Identifies Precancers among Histologically Subdiagnostic Endometrial Lesions

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)618-629
Number of pages12
JournalAmerican Journal of Surgical Pathology
Volume47
Issue number5
DOIs
StatePublished - May 1 2023

Keywords

  • Arid1a
  • Mlh1
  • Pax2
  • Pten
  • atypical hyperplasia
  • biomarkers
  • endometrial cancer
  • endometrial precancer
  • endometrioid intraepithelial neoplasia
  • β-catenin

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'β-catenin, Pax2, and Pten Panel Identifies Precancers among Histologically Subdiagnostic Endometrial Lesions'. Together they form a unique fingerprint.

Cite this