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 endogenous factors such as glucocorticoids, interferon, interleukin-1 and vitamin D. Several lines of evidence show that MT may play a role in carcinogenesis. 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. Correlation between MT expression and HLA-DR antigen expression, p53, proliferation indices (PCNA and MIBI) as well as the various clinicopathological parameters, such as age, sex, squamous metaplasia, tumor grade, stage and recurrence were studied. In a semiquantitative analysis MT expression (> 10% of neoplastic cells) was observed in 12.7%, focal MT positivity in 11.1% and almost completely lack of MT expression in 76.2% of tumors. The incidence of MT expression was significantly higher (p=0.0002) in cases with high pathological tumor grades. MT values were significantly correlated with tumor stage (p=0.0009). A statistically significant positive correlation between 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.
Ioachim
E E
EE
Department of Pathology, Medical School, University of Ioannina, Greece. Ioachime@otenet.gr
Charchanti
A V
AV
Stavropoulos
N E
NE
Athanassiou
E D
ED
Michael
M C
MC
Agnantis
N J
NJ
D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism*; D002455:Cell Division; D000939:Epitopes; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000737:chemistry; D008875:Middle Aged; D020033:Protein Isoforms; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006684:HLA-DR Antigens; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53; D008668:Metallothionein