Abstract
BACKGROUND: Metastatic Müllerian carcinomas, including endometrial and ovarian adenocarcinomas, are challenging to diagnose due to factors like similar malignancies, insufficient clinical history, multiorgan dissemination, and small tumor specimens. Immunohistochemistry (IHC) stains are commonly used to identify these cancers. PAX8 is a widely used IHC marker with varying sensitivity levels for different types of gynecologic carcinomas. SOX17, a transcription factor involved in embryonic differentiation and development, has high specificity for ovarian and endometrial carcinomas but is weakly expressed in other epithelial neoplasms. METHODS: . 56 endometrial carcinomas cases,56 ovarian cancer case and 56 cases of non-gynecological cancer, were subjected to immunohistochemical (IHC) analysis of SOX17 and PAX8. RESULTS: In endometrial carcinomas, PAX8-high/SOX17-high co-expression strongly favored endometrioid histology (90% vs. 68.8%, p = 0.04), while ovarian high-grade serous carcinomas commonly expressed PAX8 (78.9% high) with heterogeneous SOX17 expression (47.4% high). Notably, double-negative PAX8/SOX17 status completely excluded Müllerian origin in metastases from colorectal, breast, and pulmonary primary tumors (100% specificity), though renal (all PAX8+) and thyroid neoplasms (63.6% PAX8+) required additional markers for distinction. Statistical analyses confirmed subtype-specific trends (p < 0.05 for all applicable comparisons) with loss of SOX17 associated with aggressive histotypes (25% negative in serous versus 10% in endometrioid). CONCLUSIONS: Müllerian carcinomas can be distinguished from non-gynecological metastases using PAX8 and SOX17 immunohistochemistry, with PAX8-high/SOX17-high patterns strongly indicating endometrioid differentiation and double-negative results excluding gynecologic origin with consistency in colorectal, breast, and pulmonary carcinomas. Renal and thyroid carcinomas are the diagnostic traps on the basis of PAX8 expression and require additional markers for final classification in metastatic workups.