Abstract
BackgroundThe 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 resultsExpressions 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).ConclusionImmunohistochemical 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.
Highlights
Molecular chaperones of the Hsp90 (90-kDa heat shock protein) family are involved in cancer development and malignant progression
tumor necrosis factor receptor associated protein 1 (TRAP1) alone is significantly associated with chemotherapy response and overall survival, rendering TRAP1 as interesting scientific and therapeutic target
We have evaluated the expression of estrogen receptor α (ERα) in epithelial ovarian carcinoma (EOC) together with the expression of TRAP1, that has been described to be up-regulated in vitro in ER positive ovarian cancer cells exposed to estrogen [9]
Summary
Molecular chaperones of the Hsp (90-kDa heat shock protein) family are involved in cancer development and malignant progression. TRAP1/Hsp (tumor necrosis factor receptor associated protein 1), a paralogue of the Hsp family, has been recently described as a molecular marker and novel therapeutic target in local and metastatic prostate cancer [1]. Trying to understand the mechanisms involved in cancer progression and chemotherapy resistance in epithelial ovarian carcinoma (EOC), the role of heat shock proteins, including TRAP1, has just started to be investigated [4,5,6]. TRAP1, described to be involved in apoptosis evasion, was observed to be significantly up-regulated in Cisplatin resistant ovarian tumor cell lines [8]. 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. We investigated the importance of TRAP1 together with ERα in regard to clinicopathological parameters, chemotherapy response, and survival
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