Authors' Reply

We are pleased to respond to the interesting comments of Dr Stewart concerning the molecular subtyping of ovarian endometrioid carcinomas. We recently published a study on epithelial ovarian cancer in which we concluded that a number of high-grade endometrioid carcinomas may, in effect, be better classified as high-grade serous carcinoma. We reported that these tumours typically are reactive for nuclear WT1 protein by immunohistochemistry. Our diagnostic findings reflected the correlative nature of gene expression data and immuno-phenotyping (WT1+/p53+/CTNNB1−) for high-grade serous and high-grade endometrioid tumours 1. Dr Stewart raises a number of interesting observations on this subject, with an emphasis on low-grade endometrioid tumours. Stewart et al reported that 4/41 low-grade endometrioid tumours displayed nuclear localized WT1 protein 2. We also reported that 4/18 grade 1 endometrioid tumours were WT1-positive 1. While these observations are interesting, and the nature of low-grade WT1-positive tumours should be pursued by further study, our investigation focused on the molecular classification of poorly differentiated high-grade tumours. Another observation reported by Stewart et al is that nuclear WT1 protein expression was associated with a lack of concomitant endometriosis in a subset of low-grade endometrioid carcinomas 2. As surgical pathology reporting for endometriosis was not available for the entirety of our dataset, we cannot confirm this association. When reporting was available for our cohort, endometriosis was found in both WT1-negative (6/24) and WT1-positive (2/16) groups. However, the correlation was not significant (p = 0.43, Fisher's exact test). Although it is tempting to speculate that WT1-positive low-grade endometrioid tumours may arise from the surface epithelium as suggested by Dr Stewart, our study is not designed to address this question. Furthermore, we point out in our discussion that WT1 positivity is also associated with Fallopian tube epithelium and tubal intraepithelial carcinoma, currently debated as a candidate precursor to high-grade serous carcinoma of the ovary 3, 4. Though we did not document morphological variants of low-grade endometrioid carcinoma in our study, it should be noted that in some instances the differential diagnosis of a WT1-expressing endometrioid carcinoma with Sertoliform features versus a WT1-expressing Sertoli cell tumour may be diagnostically challenging 5-7. The issue of WT1-positive low-grade endometrioid tumours requires further investigation in order to be resolved. It would be advantageous to examine these putative low-grade endometrioid variants using an integrated gene expression and immunohistochemical approach to discern the true nature of the relationship.