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

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

SUBMITTER: Aust S 

PROVIDER: S-EPMC3533746 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature