Genetic analysis of the susceptibility loci associated with carcinogenesis, invasion and metastasis of oral squamous cell carcinoma and establishment of an evaluation system for the carcinoma based on the genetic information

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To establish a more accurate evaluation system of malignancy of oral squamous cell carcinoma (SCC), we examined loss of heterozygosity (LOH) and microsatellite instability (MSI) in SCCs. As a result, LOH and/or MSI were observed in the loci including XPA, XPB, XPC, XPD, XPE, XPF, XPG, CSB, p53, FHIT, APC, BRCAI, BRCA2, DCC, 3p14.1-12, 3p21.1-14.2, 3p24.1, 3p25, 8p21.1-11.2, 9p22, 9q32-33, etc. Although the meaning of genetic abnormalities at these loci is not clear, these genetic deletion and instability suggests deficiency of genetic repair of the patients. Consequently analyses of genetic delection and instability in the carcinoma cells may yeild useful information concerning recurrence of the carcinoma and possibility of multiple cancer. In addition to the LOH and MSI analyses, we also examined expression of ATP7B, UPase, and Pin1 molecule in SCCs that might be associated with clinical outcome of SCCs. The results of our study suggested that high levels of ATP7B expression in SCC are associated with unfavoralbe clinical outcome of patients with SCCs treated with cisplatin-based chemotherapy. ATP7B expression may be a preoperative indicator for a choice of cisplatin in some patients. The UPase study revealed that UPase immunostaining was associated with lymph node metastasis and was found to be a prognostic factor. As a result of the Pin1 study, it was shown that Pin1 is overexpressed in SCC and its level correlates with cyclin D level. The findings indicate that Pin1 is related to oncogenesis of SCC.