Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer -A study of the OVCAD consortium
Aust, Stefanie × Bachmayr-Heyda, Anna Tong, Dan Darb-Esfahani, Silvia Denkert, Carsten Chekerov, Radoslav Sehouli, Jalid Mahner, Sven Van Gorp, Toon Vergote, Ignace Speiser, Paul Horvat, Reinhard Zeillinger, Robert Pateisky, Petra Pils, Dietmar #
Molecular Cancer vol:11
ABSTRACT: BACKGROUND: The role of the tumor necrosis factor receptor associated protein 1 (TRAP1) -- supposed to be involved in protection of cells from apoptosis and oxidative stress -- has just started to be investigated in ovarian cancer. TRAP1 has been shown to be estrogen up-regulated in estrogen receptor alpha (ERalpha) positive ovarian cancer cells. The clinical impact of TRAP1 is not clear so far and the significance of ERalpha expression as therapeutic and prognostic marker is still controversial. Therefore, we investigated the importance of TRAP1 together with ERalpha in regard to clinicopathological parameters, chemotherapy response, and survival.Methods and resultsExpressions of TRAP1 and ERalpha were evaluated by immunohistochemical staining of tissue microarrays comprised of 208 ovarian cancer samples. TRAP1 was highly expressed in 55% and ERalpha was expressed in 52% of all cases. High TRAP1 expression correlated significantly with ERalpha (p < 0.001) but high TRAP1 expression was also found in 42% of ERalpha negative cases. High TRAP1 expression correlated significantly with favorable chemotherapy-response (HR = 0.48; 95%CI 0.24-0.96, p=0.037) and showed a significant impact on overall survival (OS) (HR = 0.65; 95%CI 0.43-0.99, p = 0.044). ERalpha expression was a favorable prognostic factor for OS in univariate and multivariate analyses. Interestingly, the combined pattern (ERalpha positive and/or TRAP1-high) revealed the strongest independent and significant positive influence on OS (HR = 0.41; 95%CI 0.27-0.64). CONCLUSION: Immunohistochemical evaluation of TRAP1 together with ERalpha provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival, rendering TRAP1 as interesting scientific and therapeutic target.