Localization of metallothionein in urothelial carcinoma of the human urinary bladder: An immunohistochemical study including correlation with HLA-DR antigen, p53, and proliferation indices

Metallothionein (MT) is a low-molecular-weight cysteine-rich protein, which has the ability to bind and sequestrate heavy metal ions. Synthesis of MT is induced in a variety of tissues by these metal ions, as well as by endog enous factors such as glucocorticoids, interferon, interleukin-1 and vitami n D. Several lines of evidence show that MT may play a role in carcinogenes is. In this study MT expression was detected immunohistochemically, using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms, in a series of 63 cases of urothelial carcinomas of the urinary bladder. C orrelation between MT expression and HLA-DR antigen expression, p53, prolif eration indices (PCNA and MIBI) as well as the various clinicopathological parameters, such as age, sex, squamous metaplasia, tumor grade, stage and r ecurrence were studied. In a semiquantitative analysis MT expression (> 10% of neoplastic cells) was observed in 12.7%, focal MT positivity in 11.1% a nd almost completely lack of MT expression in 76.2% of tumors. The incidenc e of MT expression was significantly higher (p = 0.0002) in cases with high pathological tumor grades. MT values were significantly correlated with tu mor stage (p = 0.0009). A statistically significant positive correlation be tween MT expression and the HLA-DR antigen expression (p = 0.001) was' also detected. The data suggested that MT expression was correlated with a more aggressive behavior in urothelial bladder cancer.