Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer -A study of the OVCAD consortium
1 Department of Obstetrics and Gynecology Molecular Oncology Group, Medical University of Vienna, Vienna, Austria
2 Department of Gynecology Campus Virchow Klinikum, Charite Medical University, Berlin, Germany
3 Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
4 Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium
5 Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, MUMC+ GROW School for Oncology and Developmental Biology, PO Box 5800, Maastricht, 6202AZ, The Netherlands
6 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
Molecular Cancer 2012, 11:69 doi:10.1186/1476-4598-11-69Published: 14 September 2012
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 α (ERα) positive ovarian cancer cells. The clinical impact of TRAP1 is not clear so far and the significance of ERα expression as therapeutic and prognostic marker is still controversial. Therefore, we investigated the importance of TRAP1 together with ERα in regard to clinicopathological parameters, chemotherapy response, and survival.
Methods and results
Expressions of TRAP1 and ERα were evaluated by immunohistochemical staining of tissue microarrays comprised of 208 ovarian cancer samples. TRAP1 was highly expressed in 55% and ERα was expressed in 52% of all cases. High TRAP1 expression correlated significantly with ERα (p < 0.001) but high TRAP1 expression was also found in 42% of ERα 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). ERα expression was a favorable prognostic factor for OS in univariate and multivariate analyses. Interestingly, the combined pattern (ERα positive and/or TRAP1-high) revealed the strongest independent and significant positive influence on OS (HR = 0.41; 95%CI 0.27-0.64).
Immunohistochemical evaluation of TRAP1 together with ERα provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival, rendering TRAP1 as interesting scientific and therapeutic target.