GENETIC ALTERATIONS IN TUBO-OVARIAN EPITHELIUM DURING OVARIAN NEOPLASIA

Ovarian serous carcinomas are a significant cause of female cancer mortality. Emerging evidence suggests a crucial role for the fallopian tube epithelium in the development of high-grade serous ovarian carcinomas (HGSOC), supported by shared molecular alterations like TP53 mutations. However, the precise pathogenetic mechanisms, hormonal influences, and the impact of cancer stem cells and intra-tumoral heterogeneity remain incompletely understood.

This review synthesizes existing literature, including clinical investigations, epidemiological studies, and molecular analyses, to examine the origins and development of ovarian serous carcinomas. Methodological approaches reviewed include immunohistochemistry, genetic sequencing (e.g., next-generation sequencing), RT-PCR, laser microdissection, and analysis of prophylactic salpingo-oophorectomy specimens.

The review highlights the growing evidence supporting the fallopian tube origin of HGSOC, with frequent co-occurrence of serous tubal intraepithelial carcinomas (STIC) and shared TP53 mutations. Genetic mutations in BRCA1/2, BRAF, KRAS, and PTEN contribute to tumor development. Hormonal influences, particularly estrogen and progesterone receptor expression, and the roles of cancer stem cells (CD117, CD133, CD44) and intra-tumoral heterogeneity are crucial for tumor progression and treatment response.

The fallopian tube epithelium plays a significant role in HGSOC pathogenesis. Further research is needed to elucidate the pathogenetic mechanisms, hormonal influences, and the impact of cancer stem cells and intra-tumoral heterogeneity. A comprehensive understanding of these factors will improve prevention, prognosis, and the development of tailored treatment strategies, including refined classification systems that account for tumor heterogeneity.