Early acquisition of homozygous deletions of p16/p19 during squamous cell carcinogenesis and genetic mosaicism in bladder cancer

We looked for p16/p19 deletion and p16 promoter methylation, as well as los s of 9p21 heterozygosity in pure squamous cell carcinomas (SCC), and in tra nsitional cell carcinomas (TCC) of the bladder with SCC components. Homozyg ous deletion of p16/p10 was detected in 11 of 21 (52%) cases of pure SCCs a nd in three of ten (30%) cases of TCC with SCC. Three cases of TCC with SCC had p16/p19 deletion, hypermethylation of the p16 promoter, or LOH on 9p21 only in the SCC components, suggesting that these molecular alterations oc curred preferentially in SCC. Interestingly, homozygous deletion of p16/p19 was observed in squamous metaplasia from bladder cancer patients (five of 11, 45%), showing that this change occurred in preneoplastic cells. On the other hand, p16/p19 deletions were not found in squamous metaplasias from n on cancerous patients. Hypermethylation of the p16 promoter was observed in two of 14 tumors (14%) and none of seven metaplasias examined. These data suggest that: (a) p16/p19 deletion is associated with early carcinogenesis of SCC of the bladder, and squamous metaplasia of the bladder cancer patien t has already sustained genetic changes found in cancer, and (b) genetic mo saicism occurs in cases of TCC with SCC, with the SCC component showing mor e frequent 9p21 alterations than the TCC component.