Ovarian Precancerous Lesions and Their Molecular Landscape: A Structured Scoping Review Focused on STIC and Related Precursors of Epithelial Ovarian Cancer.

Ovarian cancer remains one of the deadliest gynecologic malignancies because of late-stage diagnosis, biological heterogeneity, and the lack of effective early detection strategies. Epithelial ovarian cancer (EOC) comprises several histotypes, including high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), endometrioid ovarian carcinoma (ENOC), clear cell ovarian carcinoma (CCOC), and mucinous ovarian carcinoma (MOC), each with distinct molecular pathways and precursor lesions. In recent years, serous tubal intraepithelial carcinoma (STIC) has emerged as the principal precursor lesion of HGSC, supporting the fallopian tube origin paradigm of ovarian carcinogenesis. This structured scoping review summarizes current evidence on the molecular and cellular origins of epithelial ovarian cancer, with particular emphasis on precursor lesions, including p53 signatures, SCOUTs, STILs, cortical inclusion cysts, endometriosis-associated lesions, and borderline ovarian tumors. Particular attention is given to the molecular events that drive progression toward invasive carcinoma, including TP53 mutations, BRCA1/2 dysfunction, homologous recombination deficiency, chromosomal instability, telomere shortening, cell-cycle dysregulation, stemness-associated pathways, and inflammatory signaling. A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science to identify studies published from 2000 to 2026 that addressed ovarian cancer precursor lesions, molecular pathogenesis, and early carcinogenic mechanisms. Articles were selected for relevance to epithelial ovarian carcinogenesis, precursor biology, and translational implications. Current evidence supports substantial biological heterogeneity among precursor lesions, particularly STICs, with only a subset likely to progress to invasive HGSC. Emerging molecular approaches, including genome-wide aneuploidy profiling and integrated genomic classifiers, may improve risk stratification and facilitate earlier detection of clinically significant precursor lesions. A better understanding of precursor biology may ultimately contribute to personalized prevention strategies and improved clinical outcomes in ovarian cancer.