Transcription factors WT1 and p53 combined: a prognostic biomarker in ovarian cancer

• Published in: British journal of cancer Vol. 119; no. 4; pp. 462 - 470
• Main Authors: Carter, Julia H., Deddens, James A., Mueller, Gretchen, Lewis, Thomas G., Dooley, Mariah K., Robillard, Michelle C., Frydl, Molly, Duvall, Lydia, Pemberton, Jackson O., Douglass, Larry E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-08-2018; Nature Publishing Group
• Subjects: 631/45/880/1257; 631/67/1517/1709; Age Factors; Aged; Antigens; Biomarkers; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma; Cell Nucleus - metabolism; Drug Resistance; Epidemiology; Female; Gene Expression Regulation, Neoplastic; Humans; Invasiveness; Kaplan-Meier Estimate; Medical prognosis; Middle Aged; Molecular Medicine; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; p53 Protein; Prognosis; Retrospective Studies; Survival; Transcription factors; Tumor Suppressor Protein p53 - metabolism; Tumors; Up-Regulation; WT1 Proteins - metabolism
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-018-0191-x

Background
New approaches to ovarian cancer are needed to improve survival. Wilms’ tumour 1 (WT1) is a tumour-associated antigen expressed in many ovarian cancers. P53 is also often altered. The clinical significance of the combined expression of these two transcription factors has not been studied.
Methods
One hundred ninety-six ovarian tumours were classified histopathologically. Tumours were stained for WT1 and p53 immunohistochemically. Stains were analysed according to tumour type, grade and FIGO stage. Kaplan–Meier analyses on 96 invasive carcinomas determined whether categorical variables were related to survival.
Results
WT1 and p53 were related to ovarian tumour type, grade, FIGO stage and patient survival. Uniform nuclear p53 expression was associated with invasion and WT1 expression was associated with advanced grade, FIGO stage and poor survival. When WT1 and p53 were both in the age-adjusted Cox model, WT1 was significant while p53 was not. When we combined tumours expressing WT1 and p53, then adjusted for age and tumour subtype, the hazard ratio compared to tumours without WT1 and with normal p53 was 2.70; when adjusted for age and FIGO stage, the hazard ratio was 2.40.
Conclusions
WT1, an antigen target, is a biomarker for poor prognosis, particularly when combined with altered p53.