RESUMO
AIMS: This study aimed to determine the prevalence and clinical significance of deletions of the tumour suppressor gene PTEN in bladder cancer. METHODS AND RESULTS: A tissue microarray with 686 bladder cancers was analysed for PTEN deletions by fluorescence in-situ hybridization. PTEN mutations were analysed in nine tumours with heterozygous PTEN deletion. Heterozygous PTEN deletions were present in 16.5% of tumours and were associated with grade (P = 0.0024) and p53 status (P = 0.0141), but not linked to stage (P = 0.0965). PTEN deletions were seen in 5.8% of pTaG1, 10.9% of pTaG2, 29.0% of pTaG3, 16.7% of pT1G2, 22.2% of pT1G3, 17.7% of pT2-4G2 and 20.9% of pT2-4G3 tumours (P = 0.0235). PTEN deletions were associated significantly with recurrences in pTa tumours (P = 0.0173), progression in pT1 tumours (P = 0.0016), but not with overall or cancer-specific survival in pT2 tumours. Multivariate analyses including grade and PTEN deletions revealed that PTEN deletions but not grade were associated independently with recurrence in pTa tumours (P = 0.0377) and progression in pT1 tumours (P = 0.0030). No inactivating PTEN mutations were found. CONCLUSIONS: PTEN is linked to aggressive tumour phenotype and to unfavourable outcome in early bladder cancer. Heterozygous PTEN loss, i.e. reduced PTEN gene dosage, might be sufficient to cause aggressive tumour behaviour in bladder cancer cells.
