Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer.
OBJECTIVE
The identification of proteins that are selectively expressed in cancer and with potential to elicit an immune response is the first step towards antigen-specific immunotherapy. The Wilms tumor gene product (WT1) is inherently immunogenic and is now thought to be oncogenic. The aim of this study was to determine the expression of WT1 in epithelial ovarian cancer (EOC) and correlate with clinico-pathologic characteristics.


METHODS
WT1 expression was examined using immunohistochemistry applied on a tissue microarray of normal tissues and a panel of 100 EOC tissues. The distribution of WT1 expression and clinico-pathologic variables were analyzed. Survival probabilities were estimated by Kaplan-Meier method, and statistical significance was determined by the log-rank test.


RESULTS
WT1 expression was observed in 78/100 of specimens. The predominant expression pattern was homogenous, occurring in 66/100 (66%) of WT1-positive specimens, while 12/100 (12%) demonstrated heterogeneous staining. In normal tissues, WT1 expression was noted in kidneys, splenic capsule, Sertoli cells of the testis, and granulosa cells of the ovary. The median follow-up of the patient population was 30 months. Patients with WT1-positive tumors tended to have a higher grade (P = 0.006) and stage (P = 0.002) of tumor. However, there were no significant differences in the distribution of patients with WT1-positive tumors in relation to disease-free and overall survival.


CONCLUSIONS
Our data demonstrate that WT1 is expressed at high frequency in patients with EOC. Since WT1 demonstrates tissue-restricted expression and is inherently immunogenic, it could represent an attractive target for antigen-specific immunotherapy in EOC.
Hylander
Bonnie
B
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Repasky
Elizabeth
E
Shrikant
Protul
P
Intengan
Marilyn
M
Beck
Amy
A
Driscoll
Deborah
D
Singhal
Pankaj
P
Lele
Shashikant
S
Odunsi
Kunle
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression; D016162:Genes, Wilms Tumor; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000096:biosynthesis* / Q000235:genetics
D025721:WT1 Proteins