Correlation of Wilms' tumor 1 (WT1) expression with infiltration by regulatory T cells (Tregs) in epithelial ovarian cancer

Abstract

5578 Background: The Wilms' tumor 1 (WT1) gene is an important regulatory molecule involved in cell growth and development and has a dual effect depending upon the cell type in which it is expressed. The objectives of this study were to examine the significance of various subtypes of tumor-infiltrating lymphocytes (TILs) in patients with epithelial ovarian cancer (EOC) and to determine the relationship between TILs and WT1 expression. Methods: Formalin-fixed paraffin-embedded archival ovarian tumor specimens were obtained from 90 patients undergoing debulking surgery for EOC between 1995 and 2002. Immunohistochemistry (IHC) with anti-WT1 and anti-human CD4, CD8, CD20, CD25 were performed. The Kendall's rank correlation was used to determine the relationship between tumor infiltrating lymphocytes (TILs) and WT1 expression. Disease free (DFS) and overall survival (OS) estimates were conducted using Kaplan Meier method. Results: The median duration of follow-up was 30.6 months. Seventy-three tumor specimens (81%) expressed WT1 reactivity (focal - >75% of cells stained). The DFS was 55.3 months in WT1 negative patients compared to 26.6 months in WT1 positive patients (p = 0.49). OS was similar between the WT1 negative 44.6 months and WT1 positive 44.5 months. However, tumor positivity for WT1 correlated with higher frequencies of intraepithelial CD 8 TILs (tau = 0.197, p = 0.014) and CD4 TILs (tau = 0.233, p = 0.0039). In addition, WT1 expression also was significantly correlated with higher levels of intraepithelial Tregs (tau = 0.260, p = 0.0015). Conclusions: Although WT1 expressing tumors have higher frequencies of intraepithelial CD8 and CD4 T cells, there is also a higher frequency of Tregs that may abrogate beneficial effects of effector cells. Therefore, strategies to promote WT1 specific immunity and decrease regulatory T cell frequency and function in ovarian tumors are likely to be of benefit. No significant financial relationships to disclose.