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496 Reliable identification of endometrial precancers through Pax2, β-catenin, and Pten immunohistochemistry
  1. D Castrillon and
  2. M Aguilar
  1. UT Southwestern Medical Center, Dallas, USA


Introduction/Background*The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the WHO 2020 Classification lists loss of Pten, Pax2, or mismatch repair proteins as desirable diagnostic criteria. Other markers, most notably b-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of these markers individually—and more importantly as a group—has not been rigorously explored, raising critical questions as to which marker(s) or combination(s) thereof is the most efficient and reliable in practice.

Methodology Inclusion criteria was a diagnosis of AH/EIN on an endometrial tissue sample based on histologic features. Formalin-fixed/paraffin-embedded tissue sections from n=111 patients were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, b-catenin, Arid1a, and p53. Aberrant expression consistent with an underlying molecular defect was tabulated for each case and marker. An additional set of n=79 normal endometria was also analyzed to define optimal criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were statistically analyzed.

Result(s)*In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (82.0% of cases), Pten (51.4%), b-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The great majority of cases showed aberrant expression of ≥2 markers. The 6 markers together identified 92.8% of cases. Arid1a and Mlh1 proved to be robust and readily-scored markers, but all cases showing aberrant expression of either of these two markers was also detected by b-catenin, Pax2, or Pten.

Conclusion*A limited panel of only 3 markers (Pax2, Pten, and b-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel was practicable and robust, with at least one of the 3 markers being aberrant in 92.8% of AH/EIN.

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