Aberrant WT-1 Expression in Myoepithelial Cells of Inflammatory Breast Cancer
TN Vinh, W Wang, JS Ni, YG Man. Armed Forces Institute of Pathology and American Registry of Pathology, Washington, DC; China-Japan-Frinedship Hospital, Changchun, Jilin, China; Norman Bethune College of Medical Science, Changchun, Jilin, China
Background: Our previous studies revealed that Wilms' tumor 1 (WT-1) protein was co-expressed with smooth muscle actin (SMA) and CD31 in over 90% of the ME and endothelial cells in normal and common types of breast lesions (Li and Man. Cancer Biomarker, in press). As WT-1 has been reported to have significant paracrine inhibitory functions on tumor cell growth, our current study attempted to assess the expression status of WT-1 in ME cells of normal and pre-invasive ducts or acini adjacent to inflammatory breast cancer, a rare but one of the most aggressive form of breast malignancies.
Design: Sets of consecutive sections from 20 inflammatory human breast cancer and 20-common forms of breast malignancies were subjected to double immunohistochemistry with monoclonal antibodies to WT-1 (6F-H2; Cell Marque, Rocklin, CA), SMA, CD31, and CD34. From each case, 4-5 randomly selected duct or acinar clusters were photographed, and enlarged prints were made. The numbers of positive and negative ME and endothelial cells for each molecule were counted, scored, and statistically compared with the Pearson's Chi-squared test.
Results: In common forms of breast lesions, over 90% of the ME and endothelial cells co-expressed WT-1 and SMA or CD31. In inflammatory breast cancer, over 80% of the ME cells with strong SMA immunostaining were devoid of WT-1 expression in 19 of the 20 cases. In addition, most morphologically distinct micro-vessels that were strongly immunoreactive to CD31 or CD34 were either devoid of, or had substantially reduced, WT-1 immunoreactivities. In one case of inflammatory breast cancers, tumor cells within the lymphatic channels were strongly positive for WT-1.
Conclusions: These findings suggest that WT-1 may be an important tumor suppressor, and the loss of WT-1 in ME cell layers may lead to the aggressive behavior in epithelial cells. These findings also suggest that patients with inflammatory breast cancer may carry WT-1 related genetic alterations (Supported in part by grants DAMD17-01-1-0129, DAMD17-01-1-0130, PC051308 from Congressionally Directed Medical Research Programs, BCTR0706983 from The Susan G. Komen Breast Cancer Foundation to Dr. Yan-gao Man, and 2006CB910505 from the Ministry of Chinese Science and Technology Department to Drs. Xichen Zhang, Yan-gao Man, and Guiyuan Li).
Monday, March 9, 2009 1:00 PM
Poster Session II # 32, Monday Afternoon