Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer
Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer
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DOI：
10.3892/ol.2012.679
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发表时间：
2012-07-01
期刊：
影响因子：
2.9
通讯作者：
Mao, Wei-Min
中科院分区：
文献类型：
--
作者：
Lu, Hong-Yang;Zhang, Gu;Mao, Wei-Min
小细胞肺癌（SCLC）是一种高度侵袭性和致命的人类癌症。SCLC对化疗和放疗敏感，但长期生存率低，大多数患者最终发展为疾病进展。随着甲磺酸伊马替尼在治疗表达c-kit的胃肠道间质瘤中的成功，其在小细胞肺癌中的应用成为一种新的分子治疗方法。甲磺酸伊马替尼活性与胃肠道间质瘤c-kit基因外显子9和11突变相关。中国非小细胞肺癌中表皮生长因子受体突变的发生率高于美国和欧洲国家。中国与欧洲国家c-kit突变发生率也可能存在差异。目前，在中国尚没有关于甲磺酸伊马替尼治疗小细胞肺癌的研究。为探讨c-kit基因的表达和突变情况及其与小细胞肺癌预后的关系，采用免疫组织化学方法检测1998 - 2010年浙江省杭州市肿瘤医院手术治疗的36例小细胞肺癌患者c-kit基因的表达，并采用焦磷酸测序法检测c-kit基因第9、11外显子的突变情况。随访36例患者，分析c-kit表达及突变与预后的关系。c-kit阳性表达率为83.3%，其中弱阳性表达率为25.0%，中度阳性表达率为22.2%，强阳性表达率为36.1%。与c-kit非强染色患者相比，c-kit强染色患者的总生存期较短。c-kit基因第9、11外显子未发现突变。总之，研究结果表明，c-kit的表达是高的，和强染色是一个预后因素较差的生存。
Small cell lung cancer (SCLC) is a highly aggressive and lethal type of cancer in humans. SCLC is sensitive to chemotherapy and radiotherapy, but long-term survival is low and the majority of patients eventually develop progressive disease. With the success of imatinib mesylate in the treatment of gastrointestinal stromal tumors expressing c-kit, its use in SCLC serves as a novel molecular therapeutic approach. The activity of imatinib mesylate is correlated with the mutation of c-kit gene exons 9 and 11 in gastrointestinal stromal tumors. The incidence of epidermal growth factor receptor mutation in non-small cell lung cancer is higher in China than in the United States of America and European countries. There may be also differences in the incidence of c-kit mutation between China and European countries. At present, no study examining imatinib mesylate treatment for SCLC in China is available. To investigate the expression and mutation of c-kit and the correlation with prognosis of SCLC in China, immunohistochemistry was used to detect the expression of c-kit, and a pyrosequencing assay was used to detect mutations in c-kit exons 9 and 11 of 36 SCLC patients who received surgical treatment at the Zhejiang Cancer Hospital, Hangzhou, China, between 1998 and 2010. All 36 patients were followed up to analyze the correlation between prognosis and expression and mutation of c-kit. The incidence of c-kit-positive expression was 83.3%, including 25.0% weak staining, 22.2% moderate staining and 36.1% strong staining. The overall survival of patients with c-kit strong staining was shorter compared to patients with c-kit not strong staining. No mutation in c-kit exons 9 and 11 was detected. In conclusion, the findings showed that the expression of c-kit is high, and strong staining is a prognostic factor for worse survival.