This observational study aims to identfy genetic targets involved in the pathogenesis of gynecological tumors, with a focus on high-grade serous ovarian carcinoma. Using a triple approach - in silico, ex vivo and in vitro - the study will investigate the role of gonadotropins and their related signaling pathways in the epithelial ovarian cancers. Gene and protein expression levels will be evaluated through transcriptomic analysis, immunohistochemistry and functional assays on tumor cell lines. The goal is to uncover potential diagnostic or therapeutic targets in gynecological malignancies.

Ovarian cancer is the leading cause of death among gynecological malignanciens. High-grade serous ovarian carcinoma (HGSOC) represents the most common and aggressive subtype. Growing evidence suggests that gonadotropins and their receptors (FSHR and LHCGR), as well as membrane estrogen receptors (GPER), may play a significant role in ovarian carcinogenesis by modulating proliferative and anti-apoptotic signals. The GEN EX CO 2021 study is a monocentric, observational project conducted at AUSL-IRCCS Reggio Emilia. It is both prospective and retrospective, and it aims to identify gene expression patterns that differentiate ovarian tumor tissues from normal ovarian epithelium. The study uses a triple experimental approach:

• In silico: differentially expressed genes were identified from public datasets (GSE18521 and GSE26712) via transcriptomic analysis and pathway analysis;
• Ex vivo: mRNA and protein expression will be assessed in fresh-frozen and FFPE tissue samples from patients with HGSOC and other rare epithelial ovarian tumor subtypes (e.g., mesonephric-like, mucinous, endometrioid, clear cell);
• In vitro: functional experiments using ovarian cancer cell lines (e.g., A2780, KGN, HGL5) will evaluate the effects of gene overexpression or silencing on cell viability, apoptosis and proliferation.

Participants include both prospective cases and retrospective samples, as well as control tissues from patients undergoing surgery for benign conditions. Gene expressions will be assessed through digital PCR, while protein levels will be analyzed via immunohistochemistry. Functional studies will explore the biological impact of selected genes on tumor cell behavior. Data will be collected using a secure, coded e-CRF in compliance with ethical and privacy regulations. The ultimate goal is to identify novel molecular targets that could inform future diagnostic or therapeutic approaches in ovarian cancer.

Inclusion Criteria:

• Adult women ≥18 years old
• Histologically confirmed diagnosis of epithelial ovarian cancer (including high- grade serous, endometrioid, mucinous, clear cell, or mesonephric-like histotypes)
• Signed informed consent (for prospective cases) or ethically approved waiver (for retrospective samples)

Exclusion Criteria:

• Refusal to sign informed consent
• Diagnosis of low-grade or non-epithelial ovarian tumors
• Patients whose clinical or pathological data are unavailable or insufficient for study inclusion

Only individuals assigned female at birth are eligible to participate in this study.

Adult female patients diagnosed with epithelial ovarian cancer - including high-grade serous, endometrioid, mucinous, clear cell and mesonephric-like tumors - treated at AUSL-IRCCS Reggio Emilia, as well as women undergoing surgery for benign gynecological conditions (controls).