Utility of a PAX2, PTEN, and β-catenin Panel in the Diagnosis of Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia in Endometrial Polyps

Elena Lucas, Shuang Niu, Mitzi Aguilar, Kyle Molberg, Kelley Carrick, Glorimar Rivera-Colón, Glorimar Rivera-Colon, Katja Gwin, Yan Wang, Wenxin Zheng, Diego H. Castrillón, Diego H Castrillon, Hao Chen
The American journal of surgical pathology · 2023 · vol. 47(9) , pp. 1019–1026 · doi:10.1097/pas.0000000000002076 · PMID:37314146 · W4380576972
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A three-marker immunohistochemical panel of PAX2, PTEN, and β-catenin accurately identified atypical hyperplasia/endometrioid intraepithelial neoplasia in endometrial polyps, with aberrant expression found in 92.4% of cases.

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Abstract

The diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasm (AH/EIN) within endometrial polyps (EMPs) often poses a diagnostic conundrum. Our previous studies demonstrated that a panel of immunohistochemical (IHC) markers consisting of PAX2, PTEN, and β-catenin can be effectively utilized for the identification of AH/EIN. A total of 105 AH/EIN within EMP were analyzed using the 3-marker panel. We also evaluated these cases for the presence of morules. Benign EMP (n=90) and AH/EIN unassociated with polyp (n=111) served as controls. Aberrant expression of PAX2, PTEN, or β-catenin was observed in AH/EIN in EMP in 64.8%, 39.0%, and 61.9% of cases, respectively. At least 1 IHC marker was abnormal in 92.4% of cases. Overall, 60% of AH/EIN in EMP demonstrated abnormal results for≥2 IHC markers. The prevalence of PAX2 aberrancy was significantly lower in AH/EIN in EMP than in nonpolyp AH/EIN (64.8% vs. 81.1%, P =0.007), but higher than in benign EMP (64.8% vs. 14.4%, P <0.00001). The prevalence of β-catenin aberrancy was significantly higher in AH/EIN in EMP than in nonpolyp AH/EIN (61.9% vs. 47.7%, P =0.037). All control benign EMP demonstrated normal expression of PTEN and β-catenin. Morules were present in 38.1% of AH/EIN in EMP versus 24.3% in nonpolyp AH/EIN, and absent in benign EMP. A strong positive association was found between β-catenin and morules (Φ=0.64). Overall, 90% cases of atypical polypoid adenomyoma (n=6) and mucinous papillary proliferation (n=4) showed IHC marker aberrancy. In conclusion, the 3-marker IHC panel (PAX2, PTEN, and β-catenin) is (1) a useful tool in the diagnosis of AH/EIN in EMP; (2) PAX2 loss should be interpreted with caution and in combination with morphology and other markers.

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MeSH descriptors

Endometrial Hyperplasia Endometrial Hyperplasia Endometrial Hyperplasia Endometrial Neoplasms Endometrial Neoplasms Genital Neoplasms, Female Polyps Polyps Precancerous Conditions Precancerous Conditions beta Catenin beta Catenin Biomarkers, Tumor Biomarkers, Tumor Female Humans Hyperplasia PAX2 Transcription Factor PAX2 Transcription Factor PTEN Phosphohydrolase

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