Genetic alterations of the p16 gene in urothelial carcinoma in Taiwanese patients

Objective To measure changes in the p16 gene (MTS1, a negative regulator of cell-cycle progression at the G1 checkpoint, and a tumour suppressor gene) in urothelial carcinomas (including upper tract urothelial and bladder tum ours), and to correlate these measurements with the clinical status of such patients in Taiwan, where renal pelvic tumours comprise 47% of all kidney tumours and are more common than the average worldwide. Materials and methods Thirty-five upper tract urothelial and 61 bladder tum ours were examined for changes in p16. Deletion of the gene was assessed by Southern blot analysis and mutation analysed using polymerase chain reacti on-single strand conformation polymorphism, followed by direct sequencing. Results Of the 61 bladder carcinomas, homozygous deletion of p16 was detect ed in 12 (20%). However, a homozygous deletion was detected in 11 of 35 (31 %) upper tract urothelial carcinomas, a higher frequency than that reported for transitional cell bladder carcinomas. Deletion was detected as frequen tly in stage I tumours as in late-stage tumours, suggesting that p16 deleti on is a relatively early event in urothelial tumorigenesis. No point mutati ons were noted for p16 in any of the primary urothelial tumours. Most multi ple and recurrent tumours and metastatic nodules in individual patients con tained identical p16 genetic lesions, confirming that the tumours were prob ably monoclonal. In addition, there was a high gene dose of p16 in bladder carcinomas from patients with lymph node metastasis. Conclusion Deletion of p16 appears to be a common event in urothelial carci nomas, especially in upper tract urothelial tumours. High levels of p16 wer e detected in tumours with lymph node metastasis. It seems likely that a hi gh p16 level is associated with carcinomas of advanced stage and grade, and with poor prognosis in patients with such cancers.