P53 ACCUMULATION IN PRECURSOR LESIONS AND EARLY STAGES OF BLADDER-CANCER

Recent investigations have demonstrated alterations of the p53 tumor-s uppressor gene in a considerable number of transitional-cell carcinoma (TCC) specimens. Thus far, these investigations have been restricted to either papillary TCC or invasive bladder cancer. To obtain further information on a possible involvement of p53 in bladder cancer develop ment or tumor progression, investigations of precursor lesions and ear ly stages of this disease are required. Immunohistochemical examinatio n of 6 dysplasias and 24 carcinomas in situ (TIS) showed p53 accumulat ion, which is suggestive of p53 inactivation, in 2 (33%) and 9 (38%) o f these specimens, respectively. This ratio was similar in 9 TI lesion s (33%) and in 14 cases of muscle-infiltrative disease (35%). In papil lary tumors, p53 accumulation was observed exclusively in 3/10 moderat ely differentiated or high-grade lesions but not in 1 Ta GI tumor. The expression of p53 accumulation was a consistent finding. The examinat ion of tumor recurrences yielded either the presence or the absence of p53 overexpression in the primary and recurrent tumors of 7/8 patient s. Similarily, in multifocal TCC, p53 accumulation was also either pre sent or absent in 10/11 cases examined. These results suggest the exis tence of at least two different subgroups of TCC, with p53 accumulatio n being present in one of these groups. The observation of p53 accumul ation in dysplasia and in TIS is a prerequisite for a possible involve ment of p53 in bladder cancer carcinogenesis, although it does not pro ve this assumption.