WT1 expression associated with platinum-sensitivity and improved progression-free survival in uterine serous carcinoma

Abstract

Objectives: Wilms tumor gene 1 (WT1) expression is a hallmark of ovarian serous carcinoma (OSC) and considered to be diagnostic marker of these tumors, differentiating them from uterine serous carcinoma (USC), traditionally thought to rarely express WT1. However, recent data indicates a significant percentage of USC may express WT1, limiting its use as a differentiating marker between these two tumors. Additionally, the clinical implications of WT1 positivity in USC remain unclear. Methods: A multicenter retrospective analysis of patients with USC was conducted from 2000 - 2019. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking with archival tissue available for WT1 assessment via immunohistochemistry (IHC). Platinum-sensitive patients were defined as those recurring >6 months from last platinum-based chemotherapy. Differences in the frequencies of stage, race, chemosensitivity and sites of disease recurrence were identified using Pearson's chi-square test. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: WT1 status was evaluated in 61 patients with USC. 13 (21.3%) were positive for WT1 by IHC. Of these 61 patients, 56 had follow-up information available for review and were included in final analysis. The mean age was 67-years and the majority of patients were African American (97%). Stage distribution included 32% stage I, 5% stage II, 25% stage III and 38% stage IV. The majority of patients were designated as platinum-sensitive (63%). 36 (64%) patients recurred during the study period, 8 (62%) of the WT1 positive and 28 (65%) of the WT1 negative cohort. The most common location of recurrence was the abdomen followed by the pelvis and extra-abdominopelvic sites. There was no difference in the stage (p=0.158), race (p=0.227) or distribution of recurrence sites (p=0.581) between WT1 positive and WT1 negative tumors. Platinum-sensitivity was significantly improved in WT1 positive (92.3%) vs. WT1 negative tumors (55.8%) (p=0.016). For the entire cohort, the median PFS was 20 months and the median OS was 29 months. The median PFS and OS did not differ significantly based on WT1 status (p=0.544 and p=0.759, respectively). However, we did observe a trend towards improved PFS among WT1 positive tumors (21 vs. 16 months, respectively). On MVA, stage (p Download : Download high-res image (147KB) Download : Download full-size image Conclusions: WT1 positivity is observed in over 20% of USC, limiting its utility to differentiating OSC and USC. Additionally, WT1 status holds prognostic significance as expression was associated with improved platinum-sensitivity and a clinically significant 5-month improvement in PFS.