PAX3 and FOXO1 in High-Grade Serous Ovarian Carcinoma: Biological Roles, Immunohistochemical Expression, Emerging Biomarkers, and Clinical Implications – A Comprehensive Review

Abstract

High-grade serous ovarian carcinoma remains the most lethal gynecologic malignancy. Transcription factors PAX3 and FOXO1 regulate cellular differentiation, apoptosis, DNA repair, and survival pathways implicated in tumor progression and treatment resistance. A narrative review of the literature was conducted using PubMed and related databases to summarize and critically evaluate current evidence on the biological and potential clinical relevance of PAX3 and FOXO1 in HGSOC. Available studies indicate that PAX3 and FOXO1 participate in regulatory networks including AKT–FOXO signaling, MET activation, and epithelial–mesenchymal transition, contributing to tumorigenesis and cellular plasticity. Immunohistochemical analyses suggest increased expression of both proteins in HGSOC, with variable associations with clinicopathological parameters and patient outcomes. Mechanisms of chemoresistance—such as BRCA reversion mutations, replication fork stabilization, and tumor microenvironmental influences—may intersect with PAX3- and FOXO1-mediated pathways. In conclusion PAX3 and FOXO1 appear to be involved in key biological processes underlying HGSOC progression and therapeutic resistance, but their independent prognostic significance remains unproven. Further mechanistic and translational studies are required to clarify their potential as biomarkers or therapeutic targets.