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Published on: April 3, 2026
Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma
Shomik Sengupta1, John C Cheville, Christopher L Corless
1Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
Purpose:
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.
Materials And 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.
Insights
KIT protein expression is rare in high-grade renal cell carcinomas (RCCs), even those with sarcomatoid features. This study found no KIT mutations, suggesting imatinib therapy is unlikely to benefit these patients.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Renal cell carcinoma (RCC) is a heterogeneous malignancy.
- Sarcomatoid differentiation in RCC is associated with aggressive behavior.
- KIT protein expression has been suggested as a potential therapeutic target in some RCCs.
Purpose of the Study:
- To determine the frequency of KIT protein expression and mutations in high-grade renal cell carcinomas (RCCs).
- To evaluate the potential efficacy of imatinib mesylate (Gleevec) in treating aggressive RCCs with sarcomatoid differentiation.
Main Methods:
- Analysis of 194 patients with high-grade RCC (nuclear grade 4) undergoing nephrectomy.
- Immunohistochemical staining for KIT protein expression on tumor tissues.
- Mutational analysis of KIT exons 9, 11, 13, and 17 using polymerase chain reaction (PCR) in KIT-positive and selected negative cases.
Main Results:
- KIT protein expression was detected in only 3.6% of high-grade RCCs, including 4.1% of those with sarcomatoid differentiation.
- No KIT mutations were identified in the KIT-expressing tumors or in randomly selected negative samples.
- Patients with KIT-positive tumors had a poor prognosis, with rapid mortality.
Conclusions:
- KIT expression is infrequent in high-grade RCCs, irrespective of sarcomatoid differentiation.
- The absence of KIT mutations suggests that imatinib therapy is unlikely to be effective for this patient group.
- Further research may be needed to identify effective targeted therapies for aggressive RCC subtypes.
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