Wilms tumor protein 1 (WT1) — Not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma

• Published in: Gynecologic oncology 2016-03, Vol.140 (3), p.494-502
• Main Authors: Taube, Eliane Tabea, Denkert, Carsten, Sehouli, Jalid, Kunze, Catarina Alisa, Dietel, Manfred, Braicu, Ioana, Letsch, Anne, Darb-Esfahani, Silvia
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Carcinoma - chemistry; Carcinoma - genetics; Disease-Free Survival; ER-α; Estrogen Receptor alpha - analysis; Female; Gene Expression; Hematology, Oncology and Palliative Medicine; High-grade serous ovarian carcinoma; Humans; Immunohistochemistry; Middle Aged; Obstetrics and Gynecology; Ovarian Neoplasms - chemistry; Ovarian Neoplasms - genetics; Prognostic marker; Reproducibility of Results; RNA, Messenger - analysis; Survival Rate; WT1; WT1 Proteins - analysis; WT1 Proteins - genetics
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2015.12.018

Abstract Aims Wilms tumor protein 1 (WT1) expression is used in gynecological pathology as a diagnostic marker of serous differentiation, and is frequently co-expressed with ER-α. Early phase studies on WT1 vaccine in gynecological cancers are ongoing. In this study we aimed to determine the prognostic value of WT1 in high-grade serous ovarian carcinoma. Methods WT1 protein expression was determined by immunohistochemistry in a cohort of 207 primary high-grade serous ovarian carcinomas. WT1 mRNA expression was evaluated in a cohort of 1137 ovarian carcinomas from publically available gene expression datasets. Results High WT1 expression was a significant positive prognostic factor in primary high-grade serous ovarian carcinoma regarding overall survival (OS, p = 0.008) and progression free survival (PFS, p = 0.015), which was independent of age, stage, and residual tumor (OS: p = 0.024, PFS: p = 0.047). The prognostic significance of immunohistochemical WT1 expression could be reproduced in an independent cohort of 72 patients. On the mRNA level the prognostic significance was validated in silico in publically available gene expression datasets including TCGA data (OS: p = 0.002, PFS: p = 0.011). WT1 expression was significantly linked to ER-α expression (p = 0.001), and tumors that co-expressed both markers (WT1 +/ER-α +) had a longer survival time than tumors of all other marker combinations (OS: p = 0.002, PFS: p = 0.013). Conclusion We present WT1 as a robust prognostic marker in high-grade serous ovarian carcinoma, which adds prognostic information to ER-α. This should be kept in mind when WT1 is used as a biomarker in the context of WT1-targeting therapies.