Expression level of Wilms tumor 1 (WT1) protein has limited prognostic value in epithelial ovarian cancer: from the Danish "MALOVA" ovarian cancer study.
OBJECTIVE
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.


CONCLUSIONS
In conclusion, based on our analyses we found that WT1 expression in clinical settings may be of limited prognostic value in Danish OC patients.
Høgdall
Estrid V S
EV
Department of Virus, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark. Hogdall@dadlnet.dk
Christensen
Lise
L
Kjaer
Susanne K
SK
Blaakaer
Jan
J
Christensen
Ib Jarle
IJ
Gayther
Simon
S
Jacobs
Ian J
IJ
Høgdall
Claus K
CK
D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D025721:WT1 Proteins / Q000096:biosynthesis*
D025721:WT1 Proteins