Burger H, den Bakker M A, Stoter G, Verweij J, Nooter K
Department of Medical Oncology, Erasmus MC, Josephine Nefkens Building (Room Be420), PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Eur J Cancer. 2003 Apr;39(6):793-9. doi: 10.1016/s0959-8049(03)00026-1.
Previous studies have shown that STI571, a selective tyrosine kinase inhibitor of c-KIT, is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumours (GIST), especially those that have activating mutations in the c-kit exon 11 that encodes the juxtamembrane (JM) domain of the c-KIT oncoprotein. We examined the prevalence of activating exon 11 c-kit mutations in 26 small-cell lung cancer (SCLC) cases in order to explore whether this disease is also a potential target for treatment with STI571. Expression of c-KIT, estimated by immunohistochemistry, was demonstrated in 14 out of 22 SCLC samples (64%); nine samples showed moderate to strong staining (41%), five samples were weakly positive (23%), whereas eight samples (36%) were negative for CD117. Next, we examined the mutational status of exon 11 of the c-kit gene, by single-stranded conformational polymorphism (SSCP) and sequencing in all of the cKIT/CD117-positive tumours. However, no activating mutations in the c-kit exon 11 were found by either technique. Apparently, c-KIT oncoprotein expression in SCLC was not correlated with activating mutations in c-kit exon 11. In analogy to GISTs, our results could imply that SCLC patients would not benefit from treatment with STI571.
先前的研究表明，STI571（一种c-KIT的选择性酪氨酸激酶抑制剂）对c-KIT/CD117阳性的胃肠道间质瘤（GIST）非常有效，尤其是那些在编码c-KIT癌蛋白近膜（JM）结构域的c-kit外显子11中具有激活突变的肿瘤。我们检测了26例小细胞肺癌（SCLC）病例中c-kit外显子11激活突变的发生率，以探讨这种疾病是否也是STI571治疗的潜在靶点。通过免疫组织化学估计，22例SCLC样本中有14例（64%）显示c-KIT表达；9个样本显示中度至强染色（41%），5个样本弱阳性（23%），而8个样本（36%）CD117阴性。接下来，我们通过单链构象多态性（SSCP）和测序检测了所有cKIT/CD117阳性肿瘤中c-kit基因外显子11的突变状态。然而，两种技术均未在c-kit外显子11中发现激活突变。显然，SCLC中c-KIT癌蛋白表达与c-kit外显子11的激活突变无关。与GIST类似，我们的结果可能意味着SCLC患者无法从STI571治疗中获益。
