Molecular diagnosis of oral cancer based on aberrant expression and structural alterations of the p53 tumor suppressor gene

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Research to develop molecular diagnostic method of squamous cell carcinoma(SCC) based on the enhanced expression and alteration of the p53 tumor suppressor gene was conducted and the following results were obtained.(1) Using PCR-SSCP and direct sequencing methods, 93% of oral SCC cell lines and 63% of tumor tissues were found to have p53 gene mutations, thus indicating that presence of p53 mutations is a good molecular diagnostic marker of SCC.(2) Immunohistochemical analysis of SCC cell lines for overexpression of p53 showed that enhanced expression was detected in cells with missense mutations while the expression was negative in cells which produce p53 with C-terminal truncation. A part of missense-mutated p53 proteins were recognized by a mutant-specific antibody PAb240. Thus, not all p53 mutations were detected by immunohistochemical method, although the method is easy and quick to analyze mutation.(3) p53 overexpression was detected in 6 out of 15 leukoplakia(LK), and LK of a patient who had oral SCC at the same region. Interestingly, LK biopsy materials of this patient had the same mutation as of SCC, indicating that LK converts to SCC.(4) No significant correlation of prognostic factors was found with biological activities of mutated p53 genes as judged from transforming activities of REF with activated ras.(5) The quick and easy method for detection of p53 gene mutations was applied for SSCP analyses. This method can be incorporated as one of diagnoses in laboratories of hospitals, since no radioactive material is used.