Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia

• Published in: Modern pathology Vol. 22; no. 1; pp. 31 - 36
• Main Authors: Schraml, Peter, Frew, Ian J, Thoma, Claudio R, Boysen, Gunther, Struckmann, Kirsten, Krek, Wilhelm, Moch, Holger
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-01-2009; Elsevier Limited
• Subjects: Adapter proteins; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cilia - pathology; Cysts; Fluorescent Antibody Technique; Hospitals; Humans; Hypoxia; Immunohistochemistry; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Laboratory Medicine; Medicine; Medicine & Public Health; Mutation; original-article; Pathology; Reverse Transcriptase Polymerase Chain Reaction; Tumors; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Switzerland; gene; renal cell carcinoma; primary cilia
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2008.132

Renal cysts and clear cell renal cell carcinoma are common clinical manifestations of people with germ-line mutations of the von Hippel–Lindau tumor suppressor gene,
VHL
. Recent cell biological evidence suggests that the
VHL
gene product, pVHL, functions to maintain the primary cilium, a microtubule-based antenna-like structure whose functional integrity is believed to have an important role in cell-cycle control. As
VHL
mutations are common in sporadic clear cell renal cell carcinoma, but not papillary renal cell carcinoma, we asked whether there is an association between
VHL
status and primary cilia
in vivo
.
VHL
status was assessed in 20 cases of clear cell renal cell carcinoma and 9 cases of papillary renal cell carcinoma by DNA sequencing and by immunohistochemical staining for the hypoxia-inducible factor-
α
target gene products CA9 and GLUT-1. Of 20, 18 clear cell renal cell carcinomas, but only 1 of 9 papillary renal cell carcinomas, displayed evidence of
VHL
inactivation. In clear cell renal cell carcinoma the frequency of ciliated tumor cells ranged from 0 to 22% (median value 7.8±6.0%), whereas cilia frequency was significantly higher (
P
<0.0001) in papillary renal cell carcinoma (range 12–83%, median value 43.3±21.3%). There was no correlation between Ki-67 staining and cilia frequency, suggesting that the observed differences between the tumor types in cilia frequency are not accounted for by differences in cellular proliferation rates and that primary cilia degeneration in sporadic clear cell renal cell carcinoma depends on
VHL
inactivation. We propose that the different ciliation status of clear cell and papillary renal cell carcinoma may contribute, at least in part, to the different biological behaviors of these tumor types.