Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma

Summary

Distinguishing renal oncocytoma from chromophobe and other renal carcinomas is essential, considering their differing biological potentials. Although renal oncocytoma is considered a benign tumor, chromophobe renal cell carcinoma has potentially malignant biological behavior. The numerous reported studies on distinguishing these 2 entities have been based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. But none of these features has proven to be reliably specific, especially in tumors with overlapping phenotypes. We report a novel immunohistochemical approach based on the expression of a recently described kidney-specific cadherin (Ksp-cadherin) for the differential diagnosis of these 2 tumors. We compared Ksp-cadherin expression in 212 renal tumors, including 102 clear cell renal carcinomas, 46 papillary renal cell carcinomas, 30 chromophobe carcinomas, 3 collecting duct carcinomas, and 31 oncocytomas. In addition, we examined the expression of epithelial membrane antigen, vimentin, CK7, and Hale's colloidal iron staining. We found that chromophobe renal cell carcinomas consistently (96.7% of cases) demonstrated a distinctive membrane pattern of Ksp-cadherin expression, whereas renal oncocytomas (3.2%), clear cell renal cell carcinomas (0%), papillary renal cell carcinomas (2.2%), and collecting duct carcinomas (0%) usually did not express Ksp-cadherin. CK7 expression was found in 90.0%, 6.5%, 7.8%, 76.1%, and 33.3% of these tumor cases, respectively. Whereas CK7 was detected in different types of renal cell carcinomas, Ksp-cadherin was expressed almost exclusively in chromophobe renal cell carcinomas. Immunohistochemical analysis of Ksp-cadherin offers a fast, reliable approach for the distinguishing between renal oncocytoma and chromophobe renal cell carcinoma that is applicable for routine pathology laboratory studies without the need for time-consuming and costly ancillary studies.

Introduction

In renal tumor pathology, it is usually possible to distinguish different types of renal neoplasms on the basis of hematoxylin and eosin-stained tissue sections alone. However, overlapping morphological characteristics can pose some difficulties in making a proper diagnosis. Typical diagnostic problems can arise in discriminating such tumors as chromophobe renal cell carcinomas, oncocytomas, and the granular variant of clear cell renal cell carcinomas [1], [2], [3]. Because oncocytomas are benign tumors, making a definite separation from renal carcinomas is essential. Various studies on distinguishing these entities have been undertaken, based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. So far, none of these features has proven applicable in the routine pathology laboratory without the need for time-consuming and costly ancillary studies.

Kidney-specific cadherin (Ksp-cadherin) is a novel, kidney-specific member of the cadherin family of cell adhesion molecules. Within the kidney, Ksp-cadherin is found exclusively in the basolateral membrane of renal tubular epithelial cells and collecting duct cells, and not in glomeruli, renal interstitial cells, or blood vessels [4]. Different cadherins, including E-cadherin, cadherin-6, and N-cadherin, have been investigated in renal cell cancers, demonstrating possible correlations of tumor dedifferentiation and the presence of lymph node metastasis with loss of cadherins [5].

The role and expression pattern of Ksp-cadherin have not yet been investigated. Accordingly, we examined 212 renal neoplasms using immunohistochemistry on routinely collected tumor tissue blocks, as well as on tissue microarrays, to identify any differences between conventional types of renal carcinomas and oncocytomas.