Immunohistochemical expression of metallothionein in benign premalignant and malignant epithelium of the larynx: Correlation with p53 and proliferative cell nuclear antigen

In this study we evaluated the immunohistochemical expression of metallothi onein (MT) in 44 squamous cell carcinomas, 14 cases of in situ carcinoma, 4 7 with epithelial dysplasia, 11 papillomas and 21 cases of keratosis. The M T expression was studied in correlation with p53 protein expression and the proliferative cell nuclear antigen (PCNA). The monoclonal antibodies E9 (a nti-MT), DO-7 (which reacts with a denaturation-resistant epitope in wild-t ype and mutant p53) and PC10 (anti-PCNA) on formalin-fixed, paraffin-embedd ed tissue were used employing the immunoperoxidase (ABC) method. The immuno histochemical localization of MT has shown its rather ubiquitous presence i n the cytoplasm and nucleus of both benign and malignant epithelial cells. In most cases the adjacent "normal" epithelium showed low positivity in the basal portion. The mean value of metallothionein expression was 35.73 in s quamous cell carcinomas, 32.21 in in situ carcinomas, 11.86 in dysplastic e pithelium, 5.10 in papillomas and 3.5 in keratosis. In carcinomas, low MT e xpression (<10% of neoplastic cells) was observed in 20.5% of the cases, mo derate (10%-50% of neoplastic cells) in 54.5% and extensive expression (>50 % of neoplastic cells) in 25% of the cases. We did not find any statistical ly significant difference of MT expression between in situ and infiltrating carcinomas, while we did observe a significant difference between carcinom as and the other groups. There was a statistically significant difference i n the PCNA values in both benign and malignant lesions, while no statistica lly significant difference was observed in p53 protein expression in the ab ove groups. A positive correlation between MT expression and the PCNA value (p < 0.0001) in the benign and malignant groups was detected. The PCNA val ue was also correlated with the p53 protein expression (p = 0.001). No corr elation was found between MT and p53 protein expression. In conclusion, the se results suggest that the MT expression may play a role in the developmen t of malignant disease of the larynx, from the early phase of laryngeal car cinogenesis, independently from the p53 expression. It is also possible to contribute to tumour cell growth, as determined by the PCNA score.