WT1 is Differentially Expressed in Serous, Endometrioid, Clear Cell, and Mucinous Carcinomas of the Peritoneum, Fallopian Tube, Ovary, and Endometrium

Abstract

The Wilms' tumor gene WT1 plays complex roles in the development of the organs of the genitourinary tract and mesothelium, as well as Wilms' tumors. Although its biologic role is still unclear, most serous carcinomas of the ovary and peritoneum, mesotheliomas, and Wilms' tumor have been shown to express WT1. A recent study, however, found no WT1 expression in serous carcinomas of the endometrium, suggesting that WT1 could be useful in identifying the primary site of serous carcinomas. We examined the expression of WT1 and p53 by immunohistochemistry in 69 cases of endometrial carcinoma (35 endometrioid, 18 clear cell, 16 serous), 68 cases of ovarian carcinoma (28 serous, 11 endometrioid, 18 clear cell, and 11 mucinous), 14 fallopian tube carcinomas (12 serous, 2 endometrioid), and 20 primary peritoneal serous carcinomas. WT1 nuclear reactivity of any extent and intensity was considered positive. Immunohistochemical stains were evaluated semiquantitatively using a four-tiered scale. Among endometrial carcinomas, WT1 immunoreactivity was seen in 10 of 16 serous, but in none of 35 endometrioid or 18 clear cell carcinomas. Among ovarian tumors, WT1 expression was seen in 24 of 28 serous and 4 of 18 clear cell carcinomas, but in none of 11 endometrioid and 11 mucinous tumors. All 12 serous carcinomas but none of 2 endometrioid carcinomas of the fallopian tube were positive for WT1. WT1 expression was seen in 19 of 20 serous primary peritoneal carcinomas. The difference in WT1 expression was highly significant between serous and other types of tumors in all sites (p<0.0001, chi-square test), although the level of WT1 expression was significantly different among serous carcinomas arising at different sites (p<0.0001, Kruskal-Wallis test). A significant positive correlation was found between the level of p53 and WT1 expression in all carcinomas combined (r = 0.3935, p<0.0001, Spearman test), but when only serous carcinomas were analyzed, the correlation between p53 and WT1 expression levels did not reach statistical significance. Our results suggest that WT1 expression in epithelial tumors of the female genital tract may be related to cell differentiation and histologic subtypes of carcinomas, rather than to primary site of origin.

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

“…Among them seven genes have been reported previously as differentially expressed in endometrial tumors. Lactotransferrin (LTF) was upregulated (Walmer et al, 1995), whereas six genes including SFRP4, DCN, IGFBP6, HGF, WT1 and WNT4 were downregulated in the endometrial tumors (Rutanen et al, 1994;Bui et al, 1997;Yoshida et al, 2002;Muller-Tidow et al, 2003;Smid-Koopman et al, 2004;Acs et al, 2004;Hrzenjak et al, 2004). Of these genes, only WT1 was been specifically associated with endometrioid cancer (Acs et al, 2004).…”

Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR)

“…70,[123][124][125][126][127]149 Most tubo-ovarian serous carcinomas exhibit diffuse nuclear positivity with WT1, whereas most uterine serous carcinomas are negative. However, there is some overlap in that a proportion of uterine serous carcinomas are WT1 positive (the percentage has varied between studies) and a small percentage of tubo-ovarian HGSCs are WT1 negative.…”

“…However, there is some overlap in that a proportion of uterine serous carcinomas are WT1 positive (the percentage has varied between studies) and a small percentage of tubo-ovarian HGSCs are WT1 negative. 70,[123][124][125][126][127] It can be summarised that, although there is some overlap, diffuse WT1 positivity in a serous neoplasm favours a tubo-ovarian origin. In contrast, negative staining is a pointer towards a primary uterine neoplasm.…”

Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma

“…7 While possible explanations for this include the use of a different antibody (monoclonal vs polyclonal) and variation in antibody dilution and antigen retrieval methods compared to other studies, the observation that the degree of WT1 staining in ovarian serous carcinomas in our study is comparable to those previously reported in. [16][17][18][19][20] This suggests that the lack of sensitivity of WT1 in our laboratory for mesothelioma is due to an as-yetunidentified variable external to our immunohistochemical methodology (eg factors related to tissue fixation and processing) rather than a problem with the optimization of the use of the WT1 antibody itself. From a practical standpoint, this exemplifies the phenomenon of interlaboratory variability and demonstrates the utility of developing multiple potentially interchangeable and redundant markers, particularly when a panel approach is used for diagnosis.…”