W D Mojica1, R Saxena, P Starostik, R T Cheney. 1. Department of Pathology, State University of New York at Buffalo, Buffalo, NY 14203, USA. mojica@buffalo.edu
Abstract
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: The absence of mutations in exon 17 of CD117+ SCLC suggests this tumour may respond to therapy with TKI.
AIMS: 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. METHODS AND RESULTS: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. CONCLUSIONS: The absence of mutations in exon 17 of CD117+ SCLC suggests this tumour may respond to therapy with TKI.