SOX17 in Gynecologic Tumors: Biology and Diagnostic Applications

SOX17 is a developmental transcription factor that regulates endoderm formation, vascular development, germ cell specification, and tissue differentiation. Recent studies have identified SOX17 as a highly informative immunohistochemical marker and lineage-associated regulator in gynecologic pathology. This review summarizes the physiological functions of SOX17, its expression in normal and neoplastic tissues, and its expanding diagnostic and translational applications. SOX17 demonstrates high sensitivity for most ovarian and endometrial epithelial carcinomas while exhibiting substantially greater specificity than PAX8 because it is consistently absent in the vast majority of renal, thyroid, breast, pulmonary, gastrointestinal, and other nongynecologic carcinomas. These characteristics make SOX17 particularly valuable for supporting Müllerian origin in metastatic tumors and cytology specimens. Emerging evidence also supports its utility in diagnostically challenging settings, including mesonephric-like adenocarcinoma, seminomatous germ cell tumors, yolk sac tumors, angiosarcoma, and selected mesothelial proliferations, where awareness of potential diagnostic pitfalls is essential. Beyond its diagnostic role, SOX17 functions in a context-dependent manner, acting either as a tumor suppressor or as a lineage-survival transcription factor through interactions with signaling pathways such as Wnt/β-catenin and the PAX8 transcriptional network. These biological insights underscore its role in lineage maintenance, angiogenesis, and tumor progression and suggest potential therapeutic relevance. Collectively, current evidence establishes SOX17 as a lineage biomarker with both diagnostic and biologic relevance.