Department of Gynecological Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway.
Hum Pathol. 2012 Apr;43(4):529-35. doi: 10.1016/j.humpath.2011.05.022. Epub 2011 Aug 23.
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.
热休克蛋白 90（HSP90）具有抗凋亡特性，通过其伴侣活性的细胞保护功能和应激反应下的表达增加来发挥作用。本研究分析了 HSP90 在晚期卵巢癌患者胸水中的临床作用。使用免疫组织化学法检测 265 例胸水中 HSP90 蛋白的表达。分析结果与临床病理参数（包括化疗反应和生存）的相关性。此外，还研究了 HSP90 与一组先前研究的抗凋亡蛋白之间的相关性。HSP90 在 97%和 18%的标本中分别在肿瘤细胞的细胞质和核内表达。化疗后与化疗前相比，核内 HSP90 表达明显升高（P =.005），与铂类（P =.024）和紫杉醇（P =.007）的先前治疗显著相关。二线化疗后完全缓解与不完全/无缓解的患者相比，HSP90 表达在细胞质中更高（P =.016）。HSP90 表达与其他临床病理参数或生存均无相关性。化疗前，细胞质 HSP90 表达与 Bcl-2 显著相关（P =.04），化疗后与细胞质 Survivin 表达呈边缘相关（P =.05）。从原发性诊断到复发性胸水中，肿瘤进展导致 HSP90 上调。HSP90 不能为晚期卵巢癌患者提供预后数据。然而，HSP90 可能具有预测价值，预测哪些患者将受益于 HSP90 抑制剂治疗，以增强铂类和紫杉醇在复发性晚期卵巢癌患者中的疗效。我们建议 HSP90 作为该患者群体的潜在治疗靶点。
