Pass Harvey I, Lott Dan, Lonardo Fulvio, Harbut Michael, Liu Zhandong, Tang Naimei, Carbone Michele, Webb Craig, Wali Anil
Department of Surgery, Wayne State University, Karmanos Cancer Institute, John A. Dingell Veterans Hospital, Detroit, Mich, USA.
N Engl J Med. 2005 Oct 13;353(15):1564-73. doi: 10.1056/NEJMoa051185.
We investigated the presence of osteopontin in pleural mesothelioma and determined serum osteopontin levels in three populations: subjects without cancer who were exposed to asbestos, subjects without cancer who were not exposed to asbestos, and patients with pleural mesothelioma who were exposed to asbestos.
A group of 69 subjects with asbestos-related nonmalignant pulmonary disease were compared with 45 subjects without exposure to asbestos and 76 patients with surgically staged pleural mesothelioma. Tumor tissue was examined for osteopontin by immunohistochemical analysis, and serum osteopontin levels were measured by an enzyme-linked immunosorbent assay.
There were no significant differences in mean (+/-SE) serum osteopontin levels between age-matched subjects with exposure to asbestos and subjects without exposure to asbestos (30+/-3 ng per milliliter and 20+/-4 ng per milliliter, respectively; P=0.06). In the group with exposure to asbestos, elevated serum osteopontin levels were associated with pulmonary plaques and fibrosis (56+/-13 ng per milliliter) but not with normal radiographic findings (21+/-5 ng per milliliter), plaques alone (23+/-3 ng per milliliter), or fibrosis alone (32+/-7 ng per milliliter) (P=0.004). Serum osteopontin levels were significantly higher in the group with pleural mesothelioma than in the group with exposure to asbestos (133+/-10 ng per milliliter vs. 30+/-3 ng per milliliter, P<0.001). Immunohistochemical analysis revealed osteopontin staining of the tumor cells in 36 of 38 samples of pleural mesothelioma. An analysis of serum osteopontin levels comparing the receiver-operating-characteristic curve in the group exposed to asbestos with that of the group with mesothelioma had a sensitivity of 77.6 percent and a specificity of 85.5 percent at a cutoff value of 48.3 ng of osteopontin per milliliter. Subgroup analysis comparing patients with stage I mesothelioma with subjects with exposure to asbestos revealed a sensitivity of 84.6 percent and a specificity of 88.4 percent at a cutoff value of 62.4 ng of osteopontin per milliliter.
Serum osteopontin levels can be used to distinguish persons with exposure to asbestos who do not have cancer from those with exposure to asbestos who have pleural mesothelioma.
我们研究了骨桥蛋白在胸膜间皮瘤中的存在情况,并测定了三组人群的血清骨桥蛋白水平:接触石棉但无癌症的受试者、未接触石棉且无癌症的受试者以及接触石棉且患有胸膜间皮瘤的患者。
将一组69名患有石棉相关非恶性肺部疾病的受试者与45名未接触石棉的受试者以及76名经手术分期的胸膜间皮瘤患者进行比较。通过免疫组织化学分析检测肿瘤组织中的骨桥蛋白,并采用酶联免疫吸附测定法测量血清骨桥蛋白水平。
年龄匹配的接触石棉受试者与未接触石棉受试者的平均(±标准误)血清骨桥蛋白水平无显著差异(分别为30±3 ng/毫升和20±4 ng/毫升;P = 0.06)。在接触石棉的组中,血清骨桥蛋白水平升高与肺部斑块和纤维化相关(56±13 ng/毫升),但与正常影像学表现(21±5 ng/毫升)、单纯斑块(23±3 ng/毫升)或单纯纤维化(32±7 ng/毫升)无关(P = 0.004)。胸膜间皮瘤组的血清骨桥蛋白水平显著高于接触石棉组(133±10 ng/毫升对30±3 ng/毫升,P<0.001)。免疫组织化学分析显示,38例胸膜间皮瘤样本中有36例肿瘤细胞呈骨桥蛋白染色。对血清骨桥蛋白水平进行分析,比较接触石棉组与间皮瘤组的受试者工作特征曲线,在骨桥蛋白临界值为48.3 ng/毫升时,敏感性为77.6%,特异性为85.5%。将I期间皮瘤患者与接触石棉的受试者进行亚组分析,在骨桥蛋白临界值为62.4 ng/毫升时,敏感性为84.6%,特异性为88.4%。
血清骨桥蛋白水平可用于区分接触石棉但无癌症的人与接触石棉且患有胸膜间皮瘤的人。