Prevalence of KIT expression in human tumors.
OBJECTIVE
KIT is a target for imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Gastrointestinal stromal tumors (GISTs) express KIT and respond favorably to imatinib therapy. To determine other tumors in which such a molecular targeted therapy might be indicated, we investigated KIT expression in different human tumor types. Because recent studies in GISTs suggest that KIT-activating mutations predict response to imatinib therapy, we also sequenced a subset of positive tumors.


METHODS
More than 3,000 tumors from more than 120 different tumor categories were analyzed by immunohistochemistry in a tissue microarray format. Seven commercially available anti-KIT antibodies were initially evaluated. The antibody A4502 (DAKO) was selected for analysis because of a high frequency of positivity in GIST and low staining background in other tissues. To determine the frequency of KIT mutations in various tumor types, the exons 2, 8, 9, 11, 13, and 17 (where mutations previously were reported) were sequenced in 36 tumors with strong KIT expression.


RESULTS
KIT positivity was detected in 28 of 28 GISTs (100%), 42 of 50 seminomas (84%), 34 of 52 adenoid-cystic carcinomas (65%), 14 of 39 malignant melanomas (35%), and eight of 47 large-cell carcinomas of the lung (17%), as well as in 47 additional tumor types. KIT mutations were found in six of 12 analyzed GISTs, but only in one of 24 other tumors.


CONCLUSIONS
The results suggest that KIT expression occurs infrequently in most tumor types and that, with the exception of GISTs, KIT gene mutations are rare in immunohistochemically KIT-positive tumors.
Went
Philip Th
PT
Institute of Pathology, University of Basel, Basel, Switzerland.
Dirnhofer
Stephan
S
Bundi
Marcel
M
Mirlacher
Martina
M
Schraml
Peter
P
Mangialaio
Sara
S
Dimitrijevic
Sasa
S
Kononen
Juha
J
Lugli
Alessandro
A
Simon
Ronald
R
Sauter
Guido
G
D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D046152:Gastrointestinal Stromal Tumors / Q000276:immunology* / Q000628:therapy; D020869:Gene Expression Profiling; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D011743:Pyrimidines / Q000494:pharmacology
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit