Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337, Munich, Germany.
Faculty of Medicine, Institute of Pathology, LMU Munich, 80337, Munich, Germany.
J Cancer Res Clin Oncol. 2022 Feb;148(2):377-386. doi: 10.1007/s00432-021-03838-6. Epub 2021 Nov 5.
Forkhead Box Protein 3 (FoxP3) is known as a key mediator in the immunosuppressive function of regulatory T-cells (Tregs). The aim of our study was to investigate whether FoxP3-positive Tregs have the potential to act as an independent predictor in progression as well as in regression of cervical intraepithelial neoplasia, especially in patients with intermediate cervical intraepithelial neoplasia (CIN II).
Nuclear FoxP3 expression was immunohistochemically analysed in 169 patient samples (CIN I, CIN II with regressive course, CIN II with progressive course, CIN III). The median numbers were calculated for each slide and correlated with the histological CIN grade. Statistical analysis was performed by SPSS 26 (Mann-Whitney U test, Spearman's rank correlation).
An increased FoxP3 expression in CIN II with progression could be detected in comparison to CIN II with regression (p = 0.003). Total FoxP3 expression (epithelium and dysplasia-connected stroma) was higher in more advanced CIN grades (p < 0.001 for CIN I vs. CIN II; p = 0.227 for CIN II vs. CIN III). A positive correlation could be detected between FoxP3-positive cells in epithelium and total FoxP3 expression (Spearman's Rho: 0,565; p < 0.01).
Expression of FoxP3 could be a helpful predictive factor to assess the risks of CIN II progression. As a prognosticator for regression and progression in cervical intraepithelial lesions it might thereby help in the decision process regarding surgical treatment vs. watchful waiting strategy to prevent conisation-associated risks for patients in child-bearing age. In addition, the findings support the potential of Tregs as a target for immune therapy in cervical cancer patients.
叉头框蛋白 3（FoxP3）被认为是调节性 T 细胞（Tregs）免疫抑制功能的关键介质。我们的研究目的是探讨 FoxP3阳性 Tregs 是否有可能作为宫颈上皮内瘤变（CIN）进展和消退的独立预测因子，尤其是在中等级别（CIN II）的患者中。
对 169 例患者样本（CIN I、有消退过程的 CIN II、有进展过程的 CIN II、CIN III）进行核 FoxP3 表达的免疫组织化学分析。为每张幻灯片计算中位数，并与组织学 CIN 分级相关联。采用 SPSS 26 进行统计分析（Mann-Whitney U 检验、Spearman 秩相关）。
与有消退过程的 CIN II 相比，进展过程中的 CIN II 中可检测到 FoxP3 表达增加（p=0.003）。在更高级别的 CIN 分级中，总 FoxP3 表达（上皮和发育不良相关的基质）更高（CIN I 与 CIN II 相比，p<0.001；CIN II 与 CIN III 相比，p=0.227）。上皮内 FoxP3 阳性细胞与总 FoxP3 表达之间存在正相关（Spearman's Rho：0.565；p<0.01）。
FoxP3 的表达可能是评估 CIN II 进展风险的有用预测因子。作为宫颈上皮内病变消退和进展的预后指标，它可能有助于在手术治疗与观察等待策略之间做出决策，以避免锥切相关风险，从而保护生育年龄患者的利益。此外，这些发现支持 Tregs 作为宫颈癌患者免疫治疗靶点的潜力。
