Lu Hong-Yang, Zhang Gu, Cheng Qiao-Yuan, Chen Bo, Cai Ju-Fen, Wang Xiao-Jia, Zhang Yi-Ping, Wang Zeng, Lu Zhen-Yi, Xie Fa-Jun, Mao Wei-Min
Zhejiang Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology (esophagus, lung), Zhejiang Province.
Oncol Lett. 2012 Jul;4(1):89-93. doi: 10.3892/ol.2012.679. Epub 2012 Apr 12.
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.
小细胞肺癌（SCLC）是一种在人类中具有高度侵袭性和致命性的癌症类型。SCLC对化疗和放疗敏感，但长期生存率较低，大多数患者最终会发展为疾病进展。随着甲磺酸伊马替尼在治疗表达c-kit的胃肠道间质瘤方面取得成功，其在SCLC中的应用成为一种新的分子治疗方法。甲磺酸伊马替尼的活性与胃肠道间质瘤中c-kit基因外显子9和11的突变相关。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。中国和欧洲国家之间c-kit突变的发生率可能也存在差异。目前，中国尚无关于甲磺酸伊马替尼治疗SCLC的研究。为了研究中国SCLC中c-kit的表达、突变及其与预后的相关性，采用免疫组织化学检测c-kit的表达，并采用焦磷酸测序法检测2008年至2010年期间在中国杭州浙江省肿瘤医院接受手术治疗的36例SCLC患者c-kit外显子9和11的突变情况。对所有36例患者进行随访，分析c-kit的表达、突变与预后的相关性。c-kit阳性表达率为83.3%，其中弱染色占25.0%，中度染色占22.2%，强染色占36.1%。与c-kit非强染色的患者相比，c-kit强染色患者的总生存期较短。未检测到c-kit外显子9和11的突变。总之，研究结果表明c-kit的表达较高，强染色是生存较差的一个预后因素。
