Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma

Shomik Sengupta, John C. Cheville, Christopher L. Corless, Christine M. Lohse, Michael C. Heinrich, Eugene D Kwon, Horst Zincke, Michael L. Blute, Bradley C. Leibovich

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevec™) 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.

Original languageEnglish (US)
Pages (from-to)53-56
Number of pages4
JournalJournal of Urology
Volume175
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Renal Cell Carcinoma
Mutation
Neoplasms
Avidin
Biotin
Nephrectomy
Edetic Acid
Paraffin
Peroxidase
Exons
Staining and Labeling
Antigens
Polymerase Chain Reaction
Imatinib Mesylate
Antibodies
Therapeutics
Proteins

Keywords

  • Carcinoma
  • Kidney
  • Mutation
  • Protein-tyrosine kinase
  • Proto-oncogenes
  • Renal cell

ASJC Scopus subject areas

  • Urology

Cite this

Sengupta, S., Cheville, J. C., Corless, C. L., Lohse, C. M., Heinrich, M. C., Kwon, E. D., ... Leibovich, B. C. (2006). Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma. Journal of Urology, 175(1), 53-56. https://doi.org/10.1016/S0022-5347(05)00059-5

Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma. / Sengupta, Shomik; Cheville, John C.; Corless, Christopher L.; Lohse, Christine M.; Heinrich, Michael C.; Kwon, Eugene D; Zincke, Horst; Blute, Michael L.; Leibovich, Bradley C.

In: Journal of Urology, Vol. 175, No. 1, 01.2006, p. 53-56.

Research output: Contribution to journalArticle

Sengupta, S, Cheville, JC, Corless, CL, Lohse, CM, Heinrich, MC, Kwon, ED, Zincke, H, Blute, ML & Leibovich, BC 2006, 'Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma', Journal of Urology, vol. 175, no. 1, pp. 53-56. https://doi.org/10.1016/S0022-5347(05)00059-5
Sengupta, Shomik ; Cheville, John C. ; Corless, Christopher L. ; Lohse, Christine M. ; Heinrich, Michael C. ; Kwon, Eugene D ; Zincke, Horst ; Blute, Michael L. ; Leibovich, Bradley C. / Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma. In: Journal of Urology. 2006 ; Vol. 175, No. 1. pp. 53-56.
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abstract = "Purpose: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevec™) 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.",
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T1 - Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma

AU - Sengupta, Shomik

AU - Cheville, John C.

AU - Corless, Christopher L.

AU - Lohse, Christine M.

AU - Heinrich, Michael C.

AU - Kwon, Eugene D

AU - Zincke, Horst

AU - Blute, Michael L.

AU - Leibovich, Bradley C.

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N2 - Purpose: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevec™) 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.

AB - Purpose: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevec™) 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.

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KW - Kidney

KW - Mutation

KW - Protein-tyrosine kinase

KW - Proto-oncogenes

KW - Renal cell

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