Cao C-M, Yang F-X, Wang P-L, Yang Q-X, Sun X-R
Medical Laboratory Diagnosis Center, Jinan Central Hospital, Jinan, Shangdong, China.
Eur Rev Med Pharmacol Sci. 2014;18(6):833-9.
Osteosarcoma is the most common primary malignancy, mainly arising from the metaphysis of the long bones of adolescents and young adults. Its poor prognosis is strongly associated with invasion and distant metastasis. The calcium-binding protein S100A4 promotes metastasis in several experimental animal models, including osteosarcoma (OS), and S100A4 protein expression is associated with patient outcome in a number of tumor types. In the present study, we investigated the expression of S100A4 and its clinicopathologic significance in OSs.
S100A4 were examined immunohistochemically in resected OSs from 120 patients with OS to clarify their clinicopathologic significance. Multivariate survival analyses were carried out on all investigated parameters.
The immunohistochemical assays revealed that S1004A expression in osteosarcoma tissues was significantly higher than that in corresponding noncancerous bone tissues (p < 0.001). In addition, positive S100A4 expression more frequently occurred in osteosarcoma tissues with advanced clinical stage (p = 0.003), positive distant metastasis (p = 0.001) and poor response to chemotherapy (p = 0.04). In Kaplan-Meier analysis, only S100A4 positively stained cases showed a significantly decreased overall survival time and disease-free survival compared with negatively stained cases (both p < 0.001). On Cox multivariate analysis, positive S100A4 expression was an independent and significant prognostic factor to predict poor overall survival and disease-free survival (both p = 0.001).
Expression of S100A4 protein in OS may be related to the prediction of metastasis potency, response to chemotherapy and poor prognosis for osteosarcoma patients, suggesting that S100A4 may serve as a prognostic marker for the optimization of clinical treatments.
骨肉瘤是最常见的原发性恶性肿瘤,主要发生于青少年和年轻成年人长骨的干骺端。其预后较差与侵袭和远处转移密切相关。钙结合蛋白S100A4在包括骨肉瘤(OS)在内的多种实验动物模型中促进转移,并且S100A4蛋白表达与多种肿瘤类型患者的预后相关。在本研究中,我们调查了S100A4在骨肉瘤中的表达及其临床病理意义。
对120例骨肉瘤患者切除的骨肉瘤组织进行S100A4免疫组织化学检测,以阐明其临床病理意义。对所有研究参数进行多因素生存分析。
免疫组织化学检测显示,骨肉瘤组织中S1004A的表达明显高于相应的非癌性骨组织(p < 0.001)。此外,S100A4阳性表达在临床分期较晚(p = 0.003)、远处转移阳性(p = 0.001)和化疗反应较差(p = 0.04)的骨肉瘤组织中更常见。在Kaplan-Meier分析中,与阴性染色病例相比,只有S100A4阳性染色病例的总生存时间和无病生存时间显著缩短(两者p < 0.001)。在Cox多因素分析中,S100A4阳性表达是预测总生存和无病生存较差的独立且显著的预后因素(两者p = 0.001)。
骨肉瘤中S100A4蛋白的表达可能与骨肉瘤患者转移潜能的预测、化疗反应及预后不良有关,提示S100A4可作为优化临床治疗的预后标志物。