Molecular diagrostic assays for hepatic, pancreatic and gastrointestinal cancers

我们已经建立了一些肝癌、胰腺癌和胃肠道癌症的分子诊断方法。首先，为了检测HCC患者的循环传闻细胞，我们建立了利用RT-PCR检测循环血细胞中肝癌肿瘤标志物之一AFP m RNA的新方法。横断面分析显示，该AFP mRNA存在于52%的HCC患者中，尤其是肝外转移患者。我们对HCC患者预后与AFP-mRNA存在的关系进行了前瞻性研究，发现外周血中AFP mRNA的存在与未来肝外转移的发生密切相关，导致预后不良。相反，AFP mRNA的缺失表明存活率高。其次，在胰腺癌病例中，我们建立了一种使用改良等位基因特异性PCR检测胰腺液中K-ras突变的高灵敏度检测方法。通过这种方法，在胰管增生和胰腺癌患者的胰液中发现了K-ras突变。然而，半定量分析显示，胰腺癌病例中K-ras突变的数量在1-10%之间，而导管增生病例中K-ras突变的数量不到1%。此外，胰腺癌的K-ras突变模式与导管增生不同。这些分子诊断可能为恶性肿瘤的临床诊断和评价提供新的视角。

We have established several molecular diagnostic assays for hepatic-, pancreatic and gastrointestinal cancers. First, in order to detect circulating rumor cells in patients with HCC,we have established the new method for detecting AFP m RNA,one of tumor markers for HCC,in circulating blood cells using RT-PCR.Cross sectional analysis revealed that this AFP mRNA was found in 52% of patients with HCC,especially in patients presenting extrahepatic metastasis. Prospective study on prognosis of patients with HCC in relation to the presence of AFP-mRNA was conducted, indicating that the presence of AFP mRNA in peripheral blood was found to be closely related to future demonstration of extrahepatic metastsis, leading to poor prognosis. Conversely, the absence of AFP mRNA indicated a high survival rate. Second, in cases of pancreatic cancer, we have established a highly sensitive assay using modified allele specific PCR for detection of K-ras mutation in pancreatic juice. By using this procedure, K-ras mutation was found in pancreatic juice of patients with pancreatic duct hyperplasia as well as pancreatic cancer. However, semi-quantitative analysis showed the an amount of K-ras mutation in cases of pancreatic cancer ranged from 1-10%, in contrast to less than 1% in cases with ductal hyperplasia. In addition, a pattern of K-ras mutation pattern in pancreatic cancer was different from ductal hyperplasia. These molecular diagosis may provide a new sight for clinical diagnosis and evaluation of the malignant diseases.