Ki67, CD44, and FOXP3 as Prognostic Markers in Ovarian Immature Teratomas: Implications for Tumor Aggressiveness and Metastasis

Abstract

Background: Ovarian immature teratomas are rare germ cell tumours with varying neuroepithelial differentiation and malignant potential. Identifying reliable prognostic markers remains a challenge in clinical practice. This study evaluates the role of Ki67 (proliferation), CD44 (stemness), and FOXP3 (immune suppression) as key indicators of tumour aggressiveness, progression, and metastatic potential. Methods: A retrospective immunohistochemical study was conducted on 26 cases of ovarian immature teratomas diagnosed between 2015 and 2025. Tumours were graded according to the WHO classification, and Ki67, CD44, and FOXP3 expression was analysed using semi-quantitative scoring. Correlation analysis was performed between markers and tumour characteristics, including necrosis, tumour-infiltrating lymphocytes (TILs), and mitotic index. Statistical significance was determined using Spearman’s correlation, Kruskal-Wallis test, and Kaplan-Meier survival analysis. Results: Ki67 expression increased significantly with tumour grade (median: 12% in Grade 1, 35% in Grade 2, and 65% in Grade 3; p < 0.001), correlating with higher mitotic index and increased tumour aggressiveness. CD44 expression followed a similar trend (8% in Grade 1, 42% in Grade 2, 78% in Grade 3; p < 0.01), suggesting that highly proliferative tumours exhibit stem-like, invasive properties. FOXP3 expression was significantly elevated in Grade 3 tumours and metastatic cases (5% in Grade 1, 25% in Grade 2, 58% in Grade 3; p < 0.01), indicating a role in immune evasion. Correlation analysis revealed strong associations between Ki67 and CD44 (r = 0.72, p < 0.01), Ki67 and FOXP3 (r = 0.68, p < 0.01), and CD44 and FOXP3 (r = 0.65, p < 0.05), suggesting that proliferation, stemness, and immune suppression work synergistically to drive tumour progression. Conclusion: Ki67, CD44, and FOXP3 are independent prognostic markers in immature ovarian teratomas, with Ki67 linked to tumour proliferation, CD44 to stemness and invasiveness, and FOXP3 to immune evasion mechanisms. Their combined role in tumour progression and metastasis suggests potential therapeutic targets, mainly through immune-modulating and anti-stemness strategies. This study underscores the need for further research into targeted approaches for high-risk cases. It supports the inclusion of these markers in routine pathological assessment to refine prognostic stratification and treatment planning.