Kidney-specific cadherin, a specific marker for the distal portion of the nephron and related renal neoplasms

Abstract

Renal cell neoplasms are presumably derived from different cell types of the nephron. Clear cell and papillary renal cell carcinoma (RCC) are thought to be of proximal tubular origin, whereas oncocytoma and chromophobe RCC are derived from intercalated cells of distal nephron. A few molecules, such as RCC marker and CD10, have been shown to be markers for clear cell RCC and papillary RCC. Such markers are not yet available for renal tumors presumably of the distal nephron. The expression of kidney-specific (Ksp) cadherin, a recently cloned gene thought to be transcribed exclusively in the kidney, was studied in normal human kidney, as well as in 105 primary renal neoplasms, including 42 clear cell RCC, 30 papillary RCC, 13 chromophobe RCC, and 20 oncocytomas. The expression patterns were compared with those of RCC marker. The Ksp-cadherin expression was noted preferentially in distal convoluted tubules with a basolateral membrane stain in normal kidney. All 13 chromophobe RCC and 19 of 20 oncocytomas showed diffuse and strong immunoreactivity for Ksp-cadherin, while only 14% clear cell RCC and 13% papillary RCC showed focal positivity. The RCC marker expression was detected in 85%, 98%, 15% and 0% of clear cell RCC, papillary RCC, chromophobe RCC, and oncocytoma, respectively. A few clear cell RCC and papillary RCC showed dual expression of both RCC marker and Kspcadherin, which appear to have distinct histologic features. These results demonstrated high sensitivity and specificity of Ksp-cadherin for distal convoluted tubules, which can be used as adjunct for diagnosis of chromophobe RCC. Modern Pathology (2005) 18, 933-940.

The diagnostic and prognostic utility of claudin expression in renal cell neoplasms

“…17 Kidney-specific cadherin was found in one study to be almost exclusively expressed in chromophobe renal cell carcinoma, 34 however this finding was not supported by the others who found it also expressed in oncocytomas. 35 Similarly, cytokeratin 7 does not appear to show the consistent immunoreactivity in chromophobe renal cell carcinomas as suggested by some, preventing its utility for positive diagnostic differentiation from oncocytomas. 36 Inversely, RON proto-oncogene product and S100 protein were found preferentially expressed in oncocytoma warranting further investigation.…”

“…[28][29][30][31][32][33][34][35][36][37][38] Renal cell carcinoma marker antibody, CD10, glutathione S-transferase-a and others have shown specificity for clear cell renal cell carcinoma, 28,29 a-Methylacyl CoA racemase is expressed in papillary renal cell carcinoma, 30 whereas parvalbumin, b-defensin 1 and most recently KIT are used as markers for chromophobe renal cell carcinoma and oncocytoma. [31][32][33] However a marker with sufficient specificity to differentiate between chromophobe renal cell carcinoma and oncocytomas has not yet been unequivocally established.…”

Single cell dissection of early kidney development: multilineage priming

“…7, blue diamonds). Another cadherin, Cdh16, is a marker of the distal tubule (Shen et al, 2005). Thirteen of the 58 RV cells expressed Cdh16 (Fig.…”

Primary Cell Cultures from Human Renal Cortex and Renal-Cell Carcinoma Evidence a Differential Expression of Two Spliced Isoforms of Annexin A3

“…In RCC cultures, instead, about 93% of cells were CD13-positive and did not evidence any detectable signal for calbindin ( Figure 1A), in accord with the proximal tubular origin of RCCcc and RCCpap. 24 Moreover, primary cultures were analyzed for the expression of CA9, a powerful marker for RCC, which is known to be expressed in most, although not all, of the malignant clear cells, in a smaller number of papillary cells and is almost undetectable in normal renal cells. 25,26 Our tested RCC cultures were positive for CA9, and the FACS analysis showed that in RCC cultures an average of about 66% of cells were CA9-positive, whereas less than 2% of cells were positive in normal cortex cultures ( Figure 1A).…”