A distinct expression pattern and point mutation of c-kit in papillary renal cell carcinomas

Abstract

KIT is expressed not only in tumors derived from hematopoietic stem cells, melanocytes, germ cells, mast cells, and interstitial cells of Cajal, but also in other malignancies such as chromophobe renal cell carcinoma. This pattern of KIT expression prompted us to investigate the expression and mutation of c-kit gene exons 9, 11, 13, 17, and intron 17 in the different subtypes of renal cell carcinomas (n ¼ 66) and non-neoplastic kidneys (n ¼ 12). We found that KIT showed strong immunoreactivity in the cytoplasm of papillary renal cell carcinomas (100%), but on the cell membranes of chromophobe renal cell carcinomas (100%). Interestingly, a specific point mutation of the c-kit intron 17 (T-4A) was found only in papillary renal cell carcinomas (94%). Our study demonstrates that the expression pattern and one mutation of c-kit may distinguish papillary renal cell carcinomas.

A distinct expression pattern and point mutation of c-KIT in papillary renal cell carcinomas

“…1 However, Lin et al and we could not identify any mutation within the juxtamembranous and tyrosine kinase domains in all cases. 1,2 The other possibility that cannot be confidently dismissed is that the antibody crossreacts with another unknown cytoplasmic epitope that bears structural similarity with KIT hence it can also be blocked by the blocking peptides.…”

Response

“…1 Our finding that KIT is expressed on the cell membrane of chromophobe renal cell carcinomas (RCCs) corresponds with other recent reports. [2][3][4][5][6] However, there are some controversies on the expression of KIT in normal renal tubular cells and papillary RCCs.…”

“…[2][3][4][5][6] However, there are some controversies on the expression of KIT in normal renal tubular cells and papillary RCCs. [1][2][3][4][5][6] In contrast to our paper, 1 Dr Pan et al proposed that KIT expression in the cytoplasm of normal renal tubular cells and papillary RCCs is due to a technical difference by using EDTA as HIER buffer. In addition, Dr Pan et al suggested that the immunoreactive KIT in the cytoplasm of normal tubular cell and papillary RCC might be an unknown protein with a structural similarity or cross-reactivity with anti-KIT antibody (DAKO, Carpinteria, CA, USA).…”

“…2 First, we would like to mention in more detail about the expression of KIT in the normal renal tubular cells. 1 In fact, KIT was expressed in the cytoplasm of the cortical distal tubules while it was expressed in the cell membrane and cytoplasm of the intercalated cells of the cortical collecting ducts. Interestingly, the membranous immunoreactivity of KIT was enhanced in the basal side of cell membrane of the intercalated cells (Figure 1a and b).…”

Molecular Pathogenesis of Renal Cell Carcinoma: A Review

“…Since the frequency of MET mutations in sporadic papillary RCCs is low, it is possible that other genes might be involved in this form of renal cancer. In this respect, mutations of the KIT proto-oncogene have been described in 68% of papillary RCC patients (Lin et al, 2004). However, the role of KIT in the pathogenesis of this disease needs to be confirmed by functional studies.…”