Expression level of Wilms tumor 1 (WT1) protein has limited prognostic value in epithelial ovarian cancer From the Danish "MALOVA" Ovarian Cancer Study

Objectives.: To determine the WT1 expression level in tumor tissues from 774 women with an epithelial ovarian tumor. Secondly, to evaluate whether WT1 tissue expression levels correlate with clinico-pathological parameters and finally to investigate the prognostic value of WT1 expression levels in ovarian cancer (OC) patients. Methods.: Using tissue array we analyzed the WT1 expression level in tissues from 186 women with Low Malignant Potential tumors (LMP) (160 stage I, 5 stage II and 21 stage III) and 560 OC patients (160 stage I, 60 stage II, 289 stage III and 51 stage IV). Results.: Using 10% as cut-off level for WT1 overexpression an overall of 19% LMPs and 17% carcinomas, respectively, were found positive. For both, a higher proportion of positive tumors was found in the serous subtype compared to other histological subtypes (p < 0.0001). Kaplan-Meier survival analysis stratified by FIGO stage performed on cases using a 10% cut-off showed a shorter disease specific survival in patients with a positive WT1 expression in the tumor tissue. In a Cox survival analysis including 559 stage I to IV OC prognostic factors included FIGO stage (II vs. I: HR = 2.74, 95% CI: 1.42-5.29; III vs. II: HR = 2.23, 95% CI: 1.49-3.36; IV vs. III: HR = 1.75, 95% CI: 1.25-2.44), residual tumor after primary surgery (HR = 2.82, 95% CI: 1.87-4.26), age at diagnosis (HR = 1.02, 95% CI: 1.01-1.03), histological grade 3 of tumor versus grade 1 (grade 2 vs. grade 1: HR = 1.31, 95% CI: 0.95-1.81; grade 3 vs. grade 1: HR = 1.51, 95% CI: 1.08-2.09) and other histological tumor types vs. serous (mucinous vs. serous: HR = 0.91, 95% CI: 0.53-1.56; endometrioid vs. serous: HR = 1.02, 95% CI: 0.69-1.50; other histological types vs. serous: HR = 1.40, 95% CI: 1.01-1.95). WT1 expression (HR = 1.22, 95% CI: 0.94-1.59) had statistically no significant independent impact on survival. Conclusion.: In conclusion, based on our analyses we found that WT1 expression in clinical settings may be of limited prognostic value in Danish OC patients.