Merkel cell carcinoma: evaluation of KIT (CD117) expression and failure to demonstrate activating mutations in the C-KIT proto-oncogene - implications for treatment with imatinib mesylate.
BACKGROUND
Merkel cell carcinomas (MCCs) express the tyrosine kinase receptor KIT. However, it is not known if MCCs have activating mutations in KIT that would make them responsive to treatment with imatinib mesylate. The purpose of this article is to describe the KIT immunohistological staining pattern (CD117) of MCCs and analyze those MCCs for mutations in areas of KIT where mutations are found in gastrointestinal stromal cell tumors.


METHODS
We evaluated KIT immunostaining in nine MCCs from nine patients. In addition, we extracted DNA from the same MCCs, performed PCR amplification of C-KIT exons 9, 11, 13, and 17, and sequenced those gene products for mutations.


RESULTS
Eight of nine (88.8%) MCCs expressed KIT. No mutations were found.


CONCLUSIONS
The majority of MCCs express KIT but do not contain activating mutations in exons 9, 11, 13, or 17 of KIT. Imatinib mesylate is unlikely to provide effective therapy in MCC unless activating mutations in other areas of KIT or activating mutations in other related genes can be detected.
Swick
Brian L
BL
Department of Dermatology, University of Colorado Health Sciences Center, Aurora, CO 80045-0510, USA.
Ravdel
Larisa
L
Fitzpatrick
James E
JE
Robinson
William A
WA
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D015266:Carcinoma, Merkel Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002648:Child; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; C000715470:MAS1 protein, human; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit