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

为了建立一个更准确的口腔鳞状细胞癌(SCC)恶性程度评估系统，我们检测了SCC的杂合性缺失(LOH)和微卫星不稳定性(MSI)。结果发现，在XPA、XPB、XPC、XPD、XPE、XPF、XPG、CSB、P53、FHIT、APC、BRCA1、BRCA2、DCC、3p14.1-12、3p21.1-14.2、3p24.1、3p25、8p21.1-11.2、9p22、9q32-33等基因座均可观察到LOH和/或MSI。因此，对癌细胞中遗传缺失和不稳定性的分析可能会产生关于癌症复发和多发性癌症可能性的有用信息。除了LOH和MSI分析，我们还检测了ATP7B、UPase和Pin1分子在SCC中的表达，这可能与SCC的临床转归有关。我们的研究结果表明，鳞状细胞癌中ATP7B的高水平表达与接受顺铂为主的化疗的SCC患者的临床预后不良有关。ATP7B的表达可能是某些患者术前选择顺铂的一个指标。UPase研究表明，UPase免疫染色与淋巴结转移有关，并被发现是一个预后因素。Pin1的研究结果表明，Pin1在鳞癌中高表达，其水平与细胞周期蛋白D的水平相关。提示Pin1基因与鳞癌的发生有关。

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.