Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer -A study of the OVCAD consortium

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 (ER alpha) positive ovarian cancer cells. The clinical impact of TRAP1 is not clear so far and the significance of ER alpha expression as therapeutic and prognostic marker is still controversial. Therefore, we investigated the importance of TRAP1 together with ER alpha in regard to clinicopathological parameters, chemotherapy response, and survival. Methods and results: Expressions of TRAP1 and ER alpha were evaluated by immunohistochemical staining of tissue microarrays comprised of 208 ovarian cancer samples. TRAP1 was highly expressed in 55% and ER alpha was expressed in 52% of all cases. High TRAP1 expression correlated significantly with ER alpha (p < 0.001) but high TRAP1 expression was also found in 42% of ER alpha 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). ER alpha expression was a favorable prognostic factor for OS in univariate and multivariate analyses. Interestingly, the combined pattern (ER alpha 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 ER alpha provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival, rendering TRAP1 as interesting scientific and therapeutic target.