title: 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 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology Molecular Oncology Group, Medical University of Vienna, Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmayr-Heyda
authors.forename: Petra
authors.initials: P
authors.lastname: Pateisky
authors.forename: Dan
authors.initials: D
authors.lastname: Tong
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Radoslav
authors.initials: R
authors.lastname: Chekerov
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.forename: Toon
authors.initials: T
authors.lastname: Van Gorp
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Paul
authors.initials: P
authors.lastname: Speiser
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047628:Estrogen Receptor alpha; D018841:HSP90 Heat-Shock Proteins; C092306:TRAP1 protein, human