Association of cancer-associated fibroblasts and survival in malignant ovarian neoplasms

Objective: The aims of the study were to compare the stromal immunostaining of smooth muscle alpha-actin ($\alpha$-SMA) and fibroblast activation protein-$\alpha$ (FAP) between borderline ovarian tumors and epithelial ovarian cancer, and to evaluate their association in overall survival (OS) and disease-free survival (DFS) in patients with ovarian cancer. Methods: Patients diagnosed with malignant (n = 28) and borderline ovarian tumors (n = 18) were evaluated. Immunohistochemical study of stromal $\alpha$-SMA and FAP was carried out. The comparison of immunostaining between borderline and malignant ovarian tumors was performed using Fisher’s exact test. Survival was assessed by the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed by Cox regression. The differences were considered significant for p $<$ 0.05. Results: Evaluating stromal FAP, stronger immunostaining (2 and 3) was more often found in epithelial ovarian cancer than in borderline ovarian tumors (p = 0.0331). There was no statistical significance in the assessment of $\alpha$-SMA. Evaluating only patients with epithelial ovarian cancer, there was a higher OS in patients with stromal $\alpha$-SMA immunostaining 3 (p = 0.017). There was no statistical significance when evaluating OS and DFS in patients with stromal FAP immunostaining, nor evaluating DFS in patients with $\alpha$-SMA stromal immunostaining 3. After multivariate analysis, patients with stromal $\alpha$-SMA immunostaining 3 had higher OS compared to immunostaining 0, 1 or 2 [OR (95% CI) = 0.107 (0.018–0.649), p = 0.015]. Conclusion: Stronger FAP immunostaining was more often found in epithelial ovarian cancer than in borderline ovarian tumors. In epithelial ovarian cancer, there was a higher OS in patients with stromal $\alpha$-SMA immunostaining 3.

Epithelial ovarian cancer; Borderline ovarian tumors; Smooth muscle alpha-actin; Fibroblast activation protein-α; Tumor microenvironment; Overall sur-vival

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