Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma.
OBJECTIVE
RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevectrade mark) may be effective treatment for these aggressive tumors. We determined the frequency of KIT expression and mutation in a large series of high grade RCCs.


METHODS
We identified 194 patients who underwent nephrectomy for unilateral, sporadic nuclear grade 4 RCC between 1970 and 2002, including 123 with sarcomatoid differentiation. Sections from representative paraffin embedded tissue blocks were immunostained in an autostainer using ethylenediaminetetraacetic acid antigen retrieval, a polyclonal KIT antibody and the avidin-biotin peroxidase complex method. Mutational analysis was performed in all immunopositive and select negative cases by polymerase chain reaction amplification of KIT exons 9, 11, 13 and 17.


RESULTS
Only 7 tumors (3.6%) showed KIT expression, including 5 of the 123 (4.1%) with sarcomatoid differentiation. Four of the 7 tumors showed focal staining only. No mutations were identified in the 7 positive cases or in 8 randomly selected negative samples. Death from RCC occurred in all 7 patients with KIT positive tumors at a median of 0.6 years (range 0.3 to 2.3) and in 139 of 187 with KIT negative tumors at a median of 0.8 years (range 0 to 10.2).


CONCLUSIONS
KIT expression was identified in less than 5% of high grade RCCs with or without sarcomatoid differentiation but none of the tumors showed KIT mutations. These findings indicate that imatinib therapy is unlikely to be effective in patients with high grade RCC.
Sengupta
Shomik
S
Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
Cheville
John C
JC
Corless
Christopher L
CL
Lohse
Christine M
CM
Heinrich
Michael C
MC
Kwon
Eugene D
ED
Zincke
Horst
H
Blute
Michael L
ML
Leibovich
Bradley C
BC
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
D019009:Proto-Oncogene Proteins c-kit