Mojica W D, Saxena R, Starostik P, Cheney R T
Department of Pathology, State University of New York at Buffalo, Buffalo, NY 14203, USA.
Histopathology. 2005 Nov;47(5):517-22. doi: 10.1111/j.1365-2559.2005.02259.x.
To determine the frequency of point mutation in c-kit in CD117+ small cell lung cancer (SCLC). A significant proportion of SCLCs have been documented to be CD117+, thereby signifying they express the c-kit gene product. This finding suggests this tumour may be a potential target for tyrosine kinase inhibitor (TKI) agents directed at c-kit. A point mutation in exon 17 of the c-kit gene, however, can abrogate the binding of TKIs. This being the case, immunohistochemistry is necessary to identify potential candidates for treatment with TKIs, but DNA sequence analysis may need to be performed to determine if these tumours will respond.
Tumour cells of 23 cases of SCLC showing immunoreactivity for CD117 were laser capture microdissected from archived formalin-fixed paraffin-embedded tissue and the DNA isolated. PCR on exon 17 of the c-kit gene was performed and the amplified product sequenced. No point mutations were detected.
The absence of mutations in exon 17 of CD117+ SCLC suggests this tumour may respond to therapy with TKI.
确定CD117阳性小细胞肺癌（SCLC）中c-kit基因点突变的频率。已有大量文献记载相当比例的SCLC为CD117阳性，这意味着它们表达c-kit基因产物。这一发现提示该肿瘤可能是针对c-kit的酪氨酸激酶抑制剂（TKI）药物的潜在靶点。然而，c-kit基因第17外显子的点突变可消除TKI的结合。在这种情况下，免疫组织化学对于识别TKI治疗的潜在候选者是必要的，但可能需要进行DNA序列分析以确定这些肿瘤是否会产生反应。
从存档的福尔马林固定石蜡包埋组织中，对23例CD117免疫反应阳性的SCLC肿瘤细胞进行激光捕获显微切割，并提取DNA。对c-kit基因第17外显子进行PCR扩增并对扩增产物进行测序。未检测到点突变。
CD117阳性SCLC第17外显子无突变提示该肿瘤可能对TKI治疗有反应。
