β-catenin, PAX2, and PTEN Aberrancy Across the Spectrum of Endometrioid Ovarian Lesions

Abstract

Endometriosis is a common condition, with the ovary being the most common anatomic site. Endometriosis—particularly in the ovary—is associated with a risk of malignant progression, with a histologic spectrum of lesions from benign to malignant. Recently, a panel of 3 markers consisting of β-catenin, PAX2, and PTEN has been described as a potentially useful diagnostic adjunct in the diagnosis of intrauterine endometrioid neoplasia, where aberrancy for one or more of the markers is strongly associated with neoplasia. Here, we applied the panel to ovarian endometrioid lesions, including endometriosis, endometriosis with flat cytologic atypia, endometrioid borderline tumors, and endometrioid adenocarcinoma (n=85 cases in total). The incidence of aberrancy for the 3 markers increased along this putative neoplastic spectrum, arguing for a role of each of the markers in the neoplastic transformation of ovarian endometriosis. Just 1/32 (3%) of cases of nonatypical endometriosis was marker-aberrant, and this case was aberrant only for PAX2. One of 5 cases (20%) of endometriosis with atypia was marker-aberrant (both PAX2 and PTEN), supporting prior findings that some cases of flat atypia may represent bona fide precursor lesions. Of 19 endometrioid borderline tumors, 10 (53%) were aberrant for one or more markers, with PAX2 being the most frequently aberrant. Of 29 endometrioid adenocarcinomas, 28 (96.6%) were aberrant for at least 1 marker, with PAX2 again the most frequently aberrant. Patterns of aberrancy were well-preserved in areas of nonatypical endometriosis adjacent to borderline tumor or adenocarcinoma, supporting a biological origin in a common marker-aberrant precursor. The findings show that the biomarker panel could be of some diagnostic utility in the characterization of ovarian endometrioid neoplasia, such as in the diagnosis of endometrioid borderline tumor, distinguishing endometrioid from nonendometrioid lesions, or in identifying other types of early precursors at a higher risk of malignant transformation.