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Wilms tumor protein 1 (WT1)-- not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2016 Mar; Vol. 140 (3), pp. 494-502. Date of Electronic Publication: 2015 Dec 22. - Publication Year :
- 2016
-
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.<br />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.<br />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).<br />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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Biomarkers, Tumor analysis
Biomarkers, Tumor genetics
Carcinoma genetics
Disease-Free Survival
Estrogen Receptor alpha analysis
Female
Gene Expression
Humans
Immunohistochemistry
Middle Aged
Ovarian Neoplasms genetics
Reproducibility of Results
Survival Rate
WT1 Proteins genetics
Carcinoma chemistry
Ovarian Neoplasms chemistry
RNA, Messenger analysis
WT1 Proteins analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6859
- Volume :
- 140
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 26721227
- Full Text :
- https://doi.org/10.1016/j.ygyno.2015.12.018