Correlation of metallothionein expression with apoptosis in nasopharyngealcarcinoma

The expression of metallothionein (MT), an intracellular ubiquitous low mol ecular weight protein thiol with antioxidant properties, was studied in nas opharyngeal cancer (NPC) and correlated with the apoptotic index, Immunohis tochemical staining of randomly selected, formalin-fixed and paraffin-embed ded normal and malignant nasopharyngeal tissues were analysed for the expre ssion of MT using the commercially available E9 antibody directed against M T I and MT II isoforms. The corresponding apoptosis labelling indices were evaluated by the TUNEL method. Localization of MT at the ultrastructural le vel was studied by immunogold labelling. All the tumour sections (17 specim ens) showed MT-immunopositivity. A direct correlation between the percentag e of MT-positive cells and the staining intensity was noted (P < 0.001; Pea rson's r = 0.95). There was absence of cytoplasmic staining and only nuclea r staining (with localization in the nucleoplasm) was demonstrated in the t umour cells. In normal epithelium of the nasopharynx, the basal layer was s tained. An inverse relationship was observed between the level of MT expres sion and the apoptotic index in the NPC tissues (P = 0.0059; Pearson's r = -0.6380). The results suggest that overexpression of MT in NPC may protect the tumour cells from entering into the apoptotic process and thereby contr ibute to tumour expansion. Preferential localization of MT in the nuclei of NPC cells may possibly enhance radioresistance since radiotherapy is known to eradicate tumour cells by free radical-induced apoptosis. (C) 2000 Canc er Research Campaign.