Lymphocyte-activation gene 3 protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma

Abstract

Abstract Background Histological analysis has revealed the need for new treatment techniques for epithelial ovarian cancer. Immune checkpoint inhibitors may be a new therapeutic strategy for ovarian clear cell carcinoma (OCCC). Lymphocyte-activation gene 3 (LAG-3), an immune checkpoint, is a poor prognostic factor and a new therapeutic target for several malignancies. In this study, we demonstrated the correlation between LAG-3 expression and the clinicopathological features of OCCC. We evaluated LAG-3 expression in tumor-infiltrating lymphocytes (TILs) via immunohistochemical analysis using tissue microarrays containing surgically resected specimens from 171 patients with OCCC. Results The number of LAG-3-positive cases was 48 (28.1%), whereas the number of LAG-3-negative cases was 123 (71.9%). LAG-3 expression significantly increased in patients with advanced stages (P = 0.036) and recurrence (P = 0.012); however, its expression did not correlate with age (P = 0.613), residual tumor (P = 0.156), or death (P = 0.086). Using the Kaplan − Meier method, LAG-3 expression was found to be correlated with poor overall survival (P = 0.020) and progression-free survival (P = 0.019). Multivariate analysis revealed LAG-3 expression (hazard ratio [HR] = 1.86; 95% confidence interval [CI], 1.00 − 3.44, P = 0.049) and residual tumor (HR = 9.71; 95% CI, 5.13 − 18.52, P < 0.001) as independent prognostic factors. Conclusion Our study demonstrated that LAG-3 expression in patients with OCCC may be a useful biomarker for the prognosis of OCCC and could serve as a new therapeutic target.

Keywords

• Ovarian cancer
• Ovarian clear cell carcinoma
• Lymphocyte-activation gene 3
• Immune checkpoint inhibitors
• Prognosis
• Tumor-infiltrative lymphocytes