Correlation of ki67 overexpression to mutations of von Hippel-Lindau gene in clear-cell renal cell carcinoma

Background: The mutation of von Hippel-Lindau (VHL) tumor suppressor gene is closely related with tumorigenesis of renal clear cell carcinoma (RCCC). Ki67 is a specific cell nuclear antigen closely related with the cell cycle, generally appearing in the stages S, G2 and M of the cell amplification process, and it can emphasize the specific state of cell amplification very accurately. This study was to determine the mutation of VHL gene in RCCC, and explore its correlation to overexpression of Ki67. Methods: The specimens of RCCC and adjacent normal renal tissue from 60 patients were collected after surgery. Total RNA and genomic DNA were extracted from each sample. Variant exons in VHL gene were amplified by polymerase chain reaction (PCR) and sequenced, and DNA hypermethylation was detected by restriction analysis. Reverse transcription-PCR (RT-PCR) and Western blot were used to detect the expression of Ki67. RESULTS: Of the 60 specimens, 50 (83.3%) had various VHL gene mutations, 14 (23.3%) had more than 1 kind of gene mutation. Of the 57 cases of exon mutation of VHL gene, 17 (29.8%) were located in exon 1, 26 (45.6%) in exon 2, and 14 (24.6%) in exon 3. The expression of Ki67 in the 50 cases with VHL gene mutation was increased to 3-15 (5.85±1.54) times that of normal controls (P < 0.01). Conclusion: There are variant mutations of VHL gene in RCCC, which may lead to overexpression of Ki67.