title: Heat shock protein 90 is a putative therapeutic target in patients with recurrent advanced-stage ovarian carcinoma with serous effusions.
abstract: Heat shock protein 90 (HSP90) has anti-apoptotic properties exerted through its cytoprotective function of chaperone activity and increased expression in response to stress. The present study analyzed the clinical role of HSP90 in effusions from patients with advanced-stage ovarian carcinoma. HSP90 protein expression was investigated in 265 effusions using immunohistochemistry. Results were analyzed for association with clinicopathologic parameters, including chemotherapy response and survival. The correlation between HSP90 and a panel of previously-studied antiapoptotic proteins was additionally investigated. HSP90 was expressed in the cytoplasm and nucleus of tumor cells in 97% and 18% of specimens, respectively. Nuclear HSP90 expression was significantly higher in post-chemotherapy compared to pre-chemotherapy effusions (P = .005), significantly related to previous treatment with both platinol (P = .024) and paclitaxel (P = .007). Cytoplasmic HSP90 expression was significantly higher in effusions from patients with complete compared to incomplete/no response after second-line chemotherapy (P = .016). No association was found between HSP90 expression and other clinicopathologic parameters or survival. Cytoplasmic HSP90 expression was significantly associated with that of Bcl-2 in pre-chemotherapy effusions (P = .04), and marginally associated with cytoplasmic Survivin expression in post-chemotherapy effusions (P = .05). HSP90 is upregulated along tumor progression from primary diagnosis to recurrent effusion. HSP90 does not provide prognostic data in patients with advanced ovarian carcinoma effusions. However, HSP90 may be of predictive value as to who will benefit from treatment with HSP90 inhibitors to potentiate the effectiveness of platinol and paclitaxel in patients with recurrent advanced ovarian carcinoma effusions. We propose HSP90 as a potential therapeutic target in this patient group.
authors.affiliation: Department of Gynecological Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway.
authors.forename: Mari Bunkholt
authors.initials: MB
authors.lastname: Elstrand
authors.forename: Helene Tuft
authors.initials: HT
authors.lastname: Stavnes
authors.forename: Claes G
authors.initials: CG
authors.lastname: Tropé
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D015331:Cohort Studies; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016066:Pleural Effusion, Malignant / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D051017:Apoptosis Regulatory Proteins; D018841:HSP90 Heat-Shock Proteins