Diagnostic and Prognostic Value of TP53 Expression in Ovarian High-Grade Serous Carcinomas
M Kobel, A Reuss, A DuBois, S Kommoss, F Kommoss, D Gao, SE Kalloger, DG Huntsman, CB Gilks. University of Calgary/CLS, Calgary, AB, Canada; German Working Group Gynecologic Oncology, Ovary (AGO-OVAR), Wiesbaden, Germany; Vancouver General Hospital and British Columbia Cancer Agency, Vancouver, BC, Canada
Background: Data on TP53 expression and their association with outcome are controversial. TP53 expression has either been associated with poor outcome or has not shown association with prognosis, depending on the cut-off used to define overexpression and the composition of the study cohorts.
Design: We aimed to examine the association between TP53 expression and outcome restricted to high-grade serous carcinomas (N=508) from two population based cohorts from British Columbia representing cases with or without residual tumor after initial surgery, and one clinical trial cohort from Germany (AGO-OVAR-3). After tissue microarray construction, TP53 expression was assessed by immunohistochemistry using the DO-7 antibody (dilution 1:400) as completely negative, focal expression and overexpression defined with a cut-off of > 50% positive tumor cell nuclei. Complete negativity and overexpression have been shown to correlate with the mutation status of TP53. Univariate and multivariate cox regression models were used to correlate TP53 expression status with recurrence free survival.
Results: TP53 was completely negative in 30.3%, focally expressed in 12.0% and overexpressed in 57.7% of high-grade serous carcinomas, which was an inverse pattern compared to other subtypes of ovarian carcinomas, where the majority of cases showed focal expression. High-grade serous carcinomas that were completely negative for TP53 were associated with an increased risk of recurrence compared to cases with overexpression for the British Columbia cohort with no residual tumor (HR = 1.41, 95% CI 1.01- 1.98) and for a combined British columbia and German cohort (HR = 1.43, 95% CI 1.12- 1.82) in multivariable analysis including age, stage residual tumor and stratified for cohort.
Conclusions: Focal TP53 expression is an uncommon finding in high-grade serous carcinomas. Complete absence of TP53 expression is associated with an increased risk of earlier recurrence in high-grade serous carcinomas, and conversely, TP53 overexpression appears to indicate a favorable outcome in high-grade serous carcinomas. The molecular basis for this difference remains unclear.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 11:30 AM
Platform Session: Section D, Tuesday Morning