C-kit expression in sarcomatoid renal cell carcinoma: potential therapy with imatinib

• Published in: The Journal of urology Vol. 171; no. 6 Pt 1; p. 2176
• Main Authors: Castillo, Mireia, Petit, Anna, Mellado, Begoña, Palacín, Antonio, Alcover, Joan B, Mallofré, Carme
• Format: Journal Article
• Language: English
• Published: United States 01.06.2004
• Subjects: Adult; Aged; Antineoplastic Agents - therapeutic use; Benzamides; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Female; Gene Expression Regulation, Neoplastic; Humans; Imatinib Mesylate; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Male; Middle Aged; Piperazines - therapeutic use; Proto-Oncogene Proteins c-kit - genetics; Pyrimidines - therapeutic use; Sarcoma - genetics
• ISSN: 0022-5347; 1527-3792
• DOI: 10.1097/01.ju.0000127727.33232.cf

Sarcomatoid (S) renal cell carcinoma (RCC) is an uncommon subtype of RCC with a poor prognosis because of its local aggressiveness and high metastatic rate. Currently, there is no specific, effective treatment for it. A relatively nontoxic tyrosine kinase inhibitor, imatinib (STI-571) has been approved as a target therapy in neoplasms that express c-Kit. We investigated c-Kit expression in this type of tumor, which to our knowledge has not been previously described. We reviewed 215 cases of RCC diagnosed at our department from 1995 to 2002. Of the cases 20 (9.3%) were SRCC. Formalin fixed, paraffin embedded material was available in 19 cases. We performed immunohistochemical staining against c-Kit using rabbit polyclonal antihuman antibody (CD117, Dako Corp., Carpinteria, California), diluted 1:100. Its expression was evaluated in the epithelial and the spindle components. Two of the 20 SRCC cases (10%) showed no epithelial differentiation. The epithelial component was conventional RCC in 10 cases (50%), papillary RCC in 5 (25%) and chromophobe RCC in 3 (15%). A total of 16 cases (80%) presented at an advanced stage at diagnosis, namely T3 or T4 and/or metastatic disease. Immunohistochemical study showed positivity in the epithelial component only in the 3 chromophobe SRCCs. The sarcomatoid component was positive for c-Kit in 18 cases (94.7%). High c-Kit expression in SRCC in our series and the existence of a target therapy, imatinib (STI-571), against cells that express this receptor open the possibility of using this treatment for these tumors, especially in cases of advanced disease.