Abstract
BackgroundMetallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival.Patients and methodsThe immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival).ResultsPositive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival.ConclusionsThe inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter.
Highlights
Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment
The inverse correlation between MT staining intensity and tumor nuclear grade in renal cell carcinoma (RCC) suggests a role of MT in tumor differentiation process
Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter
Summary
Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. MTs are a family of heavy metal binding proteins with a large degree of sequence homology that have been described in most vertebrate and invertebrate species. They are single-chain proteins, with molecular weight of approximately 6000 Da, characterized by a very high proportion of cysteine residues (30%), resulting in several high affinity Cd and/or zinc (Zn) binding sites [3]. The potential for wider tissue distribution of MT-III was suggested by recent studies demonstrating the presence of MT-III mRNA and protein in the adult and developing human kidney [8,9]
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