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HSP60 Predicts Survival in Advanced Serous Ovarian Cancer

Hjerpe, Elisabet MD*; Egyhazi, Suzanne PhD; Carlson, Joseph MD, PhD; Stolt, Marianne Frostvik BT; Schedvins, Kjell MD§; Johansson, Hemming BSc*; Shoshan, Maria PhD; Åvall-Lundqvist, Elisabeth MD, PhD*

International Journal of Gynecological Cancer:
doi: 10.1097/IGC.0b013e318284308b
Ovarian Cancer
Abstract

Objective: Heat shock protein 60 (HSP60) plays an essential role in malignant cell survival. We evaluated the prognostic and treatment predictive value of HSP60 in advanced ovarian cancer.

Methods: Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 fulfilled the eligibility criteria, that is, International Federation of Gynecology and Obstetrics stage IIC-IV, serous/endometrioid tumors, platinum-based chemotherapy, and specimens with 50% tumor cells or greater. Heat shock protein 60 mRNA and protein expression was determined by real-time polymerase chain reaction and immunohistochemistry. We estimated the association between HSP60 and overall survival (OS) and platinum-free interval (PFI) by Cox proportional hazards models and its relationship with treatment response by Fisher’s exact test. Median follow-up was 60 months.

Results: High HSP60 mRNA expression was associated with shorter OS (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.3–8.5) and PFI (HR, 3.3; 95% CI, 1.5–7.2). Likewise, high HSP60 protein expression was associated with shorter OS (HR, 3.2; 95% CI, 1.5–7.1) and PFI (HR, 2.6; 95% CI, 1.3–5.3). Median survival for patients with high HSP60 protein expression was 31 months compared with 55 months for low expression cases (P = 0.016). The impact on OS and PFI was even stronger in the subgroup of grade 3 serous tumors. All patients with low HSP60 levels responded to first-line chemotherapy.

Conclusion: Heat shock protein 60 may identify groups of advanced serous ovarian cancer with different prognosis and treatment response.

Author Information

*Department of Oncology, Karolinska University Hospital; †Department of Oncology and Pathology, Cancer Center Karolinska CCK R8:03, Karolinska Institutet; and Departments of ‡Pathology and §Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.

Address correspondence and reprint requests to Elisabet Hjerpe, MD, Unit for Gynecologic Oncology, Department of Oncology, Karolinska University Hospital, Z500, SE-171 76 Stockholm, Sweden. E-mail: elisabet.hjerpe@karolinska.se.

This study was funded by the Swedish Cancer Society and The Cancer Research Funds of Radiumhemmet. Financial support was also provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet.

The authors declare no conflicts of interest.

Received October 20, 2012

Accepted December 20, 2012

Copyright © 2013 by IGCS and ESGO