[Molecular biology in bladder carcinoma: contributions of immunohistochemistry]

Despite the insights genetics and molecular biology have given to a better understanding of the mechanisms which lead to the onset and development of bladder carcinoma, the factors that influence its unpredictable and, at times, particularly aggressive outcome are still largely unknown. Also in bladder carcinoma the study of cellular differentiation markers has been replaced by that of genotypic alterations, and, mainly with the help of immunohistochemistry, of the expression of genes involved in cell proliferation and death, such as MTS1, TP53, Rb, c-myc, Bcl-2, c-erb-B2. So far, anyway, no independent and reliable indicator able to predict the outcome of the single tumour has been identified, and this issue seems to be best addressed by studies of the altered expression of more than one oncoprotein simultaneously. Fairly identical is the question arised by TP53 mutations, which, while worsening the evolution of advanced muscle-infiltrating tumours, hold a still unclear and debated meaning in superficial tumours. It is anyway clear that molecular analysis only may enable to reliably detect the presence of any TP53 mutations. As a matter of fact, the multiplicity of genetic mutations, the frequent transcript variations and the intrinsic limits of immunohistochemistry may explain the discrepancy between immunohistochemical and molecular analysis results, with specificity and sensitivity levels clinically not acceptable. To date, anyway, the biological and clinical meaning of this discrepancy has still to be clarified, as well as the clinical meaning, if any, of p53 overexpression in the absence of gene mutations.