Asbestos Diseases Research Institute, Bernie Banton Centre, Rhodes, New South Wales, Australia.
Cancer. 2012 Jun 1;118(11):2952-61. doi: 10.1002/cncr.26497. Epub 2011 Oct 21.
Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis remains poor. Clinical prognostic scoring systems lack precision. No prognostic tissue markers are available. Aquaporin 1 (AQP1) is a cell membrane channel involved in water transport, cell motility, and proliferation. A blocker and an agonist are available.
Two independent cohorts of MM were studied. Cohort 1 consisted of 80 consecutive patients who underwent radical surgery (extrapleural pneumonectomy [EPP]). Cohort 2 included 56 conservatively managed patients from another institution. Clinical information was obtained from files. Diagnoses were histologically verified. Immunohistochemical labeling for AQP1 was performed on tumor tissue and the percentage of positive cells was scored.
We demonstrated expression of AQP1 in normal and neoplastic mesothelium at the apical aspect of the cell, in keeping with a role in water transport. For both cohorts, expression of AQP1 by ≥50% of tumor cells was associated with significantly enhanced survival (9.4 months vs 30.4 months in EPP patients and 5 months vs 15 months in conservatively treated patients). This was independent of established prognostic factors, including histologic subtype, pathologic stage, sex, and age at time of diagnosis.
Expression of AQP1 correlated significantly with prognosis in MM, irrespective of treatment or established prognostic factors. Immunohistochemical labeling for AQP1 should be included in the routine histopathologic workup. An agonist or blocker may become useful for treatment.
恶性间皮瘤（MM）是一种侵袭性的浆膜恶性肿瘤，主要发生于胸膜。它与石棉暴露有关，在大多数工业化国家，其发病率预计将保持稳定或增加，直到 2020 年。预后仍然较差。临床预后评分系统缺乏准确性。目前尚无预后组织标志物。水通道蛋白 1（AQP1）是一种参与水转运、细胞运动和增殖的细胞膜通道。目前已有其阻滞剂和激动剂。
研究了两个独立的 MM 队列。队列 1包括 80 例连续接受根治性手术（胸膜外全肺切除术[EPP]）的患者。队列 2包括另一家机构的 56 例保守治疗患者。从病历中获取临床信息。通过组织学验证诊断。对肿瘤组织进行 AQP1 免疫组织化学标记，对阳性细胞的比例进行评分。
我们证明了 AQP1 在正常和肿瘤性间皮细胞的顶端表达，这与水转运的作用一致。对于两个队列，AQP1 在≥50%的肿瘤细胞中的表达与显著改善的生存相关（EPP 患者的 9.4 个月与 30.4 个月，保守治疗患者的 5 个月与 15 个月）。这与既定的预后因素无关，包括组织学亚型、病理分期、性别和诊断时的年龄。
AQP1 的表达与 MM 的预后显著相关，与治疗或既定的预后因素无关。AQP1 的免疫组织化学标记应纳入常规组织病理学检查。激动剂或阻滞剂可能对治疗有用。
