Analysis of mutation in the neurofiblomatosis type 2 (NF2) gene in preneoplastic and neoplastic lesion of human pleura.

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(Background and aim) It was reported high incidence of mutation in the neurofiblomatosis type 2 (NF2) gene in human malignant methothelioma. To establish a model of gene therapy with NF2 gene for malignant methothelioma, we performed genetic analysis of NF2 gene with DNA of malignant methothelioma and tumor adjacent pleura of surgically resected malignant methothelioma cases. And we also performed immunohistochemical analysis of these malignant methothelioma and malignant pleurisy cases of lung cancer to evaluate mutation of NF2 gene and biological behavior of the tumor. (Materials and Methods) Three cases of resected malignant methothelioma and 65 cases of resected lung cancer cases with subclinical pleural dissemination were examined. Tumor DNA was isolated by phenol-chloroform method and mutation of NF2 gene was evaluated by PCR-SSCP method. Immunohistochemistry was performed with C-18 and A-19 antibody for NF2 gene, MIB-1 antibody for Ki-67 antigen and DO-7 antibody for p53 oncoprotain. (Results and Conclusion) In these three cases, genomic PCR amplification was successfully obtained in the exon 3, exon 4, exon 7, exon 13 and exon 16 of NF2 gene. But no apparent mutation of NF2 gene was detected by SSCP analysis which was performed in these five exons. Immunohistochemical analysis also showed the same results with C-18 and A-19 antibodies. Ki-67 labeling index was low and negative for p53 oncoprotain in two methothelioma cases. In lung cancercases, it was disclosed Ki-67 labeling index was independent prognostic factor and correlated well with clinical course of the lung cancer cases with pleural dissemination. Further investigation with more methothelioma cases must be needed to evaluate the role of NF2 gene in malignant methothelioma patients.