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Metallothionein (MT) is a cysteine-rich protein with pleiotropic functions and a high binding affinity for heavy metals. The present study was designed to examine the relationship between MT expression and tissue zinc levels in conjunction with cell proliferation in nasopharyngeal cancer (NPC). Proliferative activity in NPC was quantified by Ki67 immunolabelling and MT expression was determined by immunohistochemistry. Total zinc and subcellular zinc fractions were analysed by flame atomic absorption spectrometry. MT immunostaining was observed in the nuclei of NPC cells, with the percentage MT immunopositivity ranging from 3.0 to 59.7%. Thirteen tumours displayed weak MT staining and the remaining 11 showed moderate to strong immunostaining. There was a significant positive correlation between MT and Ki67 positivity (P = 0.0127). Tissue zinc levels were higher in NPC as compared with benign nasopharyngeal tissues (4.800 +/- 0.4610 versus 2.889 +/- 0.4045 microgram/g dry wt tissue, respectively; P = 0.0122). Nuclear zinc levels in NPC were significantly higher than levels in membrane and cytosolic fractions (mean zinc levels 1.4840 +/- 0.1489, 0.6286 +/- 0.0789 and 0.3014 +/- 0.0250 microgram/mg protein, respectively). A linear relationship was also observed between nuclear zinc levels and MT immunostaining (P = 0.0024) as well as with Ki67 immunopositivity (P = 0.0123). Our results show that MT and zinc are correlated with proliferative activity in NPC, providing further insights into the biology of this enigmatic and aggressive tumour.