Abstract
BackgroundNew 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.MethodsOne 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.ResultsWT1 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.ConclusionsWT1, an antigen target, is a biomarker for poor prognosis, particularly when combined with altered p53.
Highlights
Epithelial ovarian cancer (OvCa) is the leading cause of death from gynaecologic cancers and has the highest mortality rate of any female reproductive cancer
We report that the combination of these two immunohistochemically (IHC) detected transcription factors and tumour-associated antigens diffusely expressed in some OvCas, varies both within and between morphologic subtypes of ovarian tumours and that IHC detection of these tumourassociated antigens in OvCa could be useful biomarkers allowing better prognostication and patient selection for newer immunologic approaches targeting Wilms’ tumour 1 (WT1) for therapy of lethal OvCa
Seventyfive percent of patients with type 2 OvCa in this study died from ovarian cancer while 40% of type 1 patients died from OvCa
Summary
Wilms’ tumour 1 (WT1) is a tumour-associated antigen expressed in many ovarian cancers. The clinical significance of the combined expression of these two transcription factors has not been studied. Stains were analysed according to tumour type, grade and FIGO stage. 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 we combined tumours expressing WT1 and p53, 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, when combined with altered p53.
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