ToxSci Advance Access published online on March 24, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj174
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1 Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202
* To whom correspondence should be addressed. The goal of this study was to determine if the expression of the MT-1/2 proteins might serve as a biomarker for the development of bladder cancer. A retrospective analysis of MT-1/2 staining was performed on 343 tissue sections from patients referred for the diagnosis of bladder cancer. The specimens were subdivided into 6 categories; benign, dysplastic, low grade cancer, high grade cancer with no evidence of invasion, high grade cancer with evidence of invasion, and carcinoma in situ. There was no expression of MT-1/2 in benign lesions and low grade cancers, a low incidence of expression in dysplastic lesions and high grade cancers with no evidence of muscle invasion, and a significantly increased incidence of MT-1/2 in high grade cancers that had invaded the underlying matrix. The expression of MT-1/2 varied in intensity from sample to sample and was focal in its expression. It was concluded from these findings that MT-1/2 may be a prognostic marker for cancers that are progressing to invade the underlying stroma of the bladder wall. The expression of MT-1/2 was also determined in a cell culture model of human urothelium that had been malignantly transformed by Cd+2 and As+3 and shown to be capable of tumor formation in nude mice. It was demonstrated that the expression of MT-1/2 in the tumor heterotransplants was similar to the pattern found in archival specimens of high grade bladder cancers. The MT-1/2 staining in the heterotransplants was focal in pattern, varied in intensity, and was highest in the less differentiated cells of the tumor. These findings indicate that the cell culture model may serve to help define the role of MT-1/2 expression in bladder cancer invasion.
Received January 31, 2006
Accepted March 21, 2006
Environmental Toxicology
Metallothionein-1 and -2 Expression in Cadmium or Arsenic Derived Human Malignant Urothelial Cells and Tumor Heterotransplants and as a Prognostic Indicator in Human Bladder Cancer
Xu Dong Zhou 1,
Donald A. Sens 1,
Mary Ann Sens 1,
Venugopal BRK Namburi 1,
Rajendra K. Singh 1,
Scott H. Garrett 1,
and
Seema Somji 1 *
Seema Somji, E-mail: ssomji{at}medicine.nodak.edu
Abstract 
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