肝硬化结节癌变的影像与细胞病理、分子表达的关系

It has been shown by researches of pathologists all over the world that carcinogenesis of liver-cirrhosis-nodule is a multiphase process: from regenerative nodule (RN) to ordinary adenomatous hyperplasia (OAH) to atypical adenomatous hyperplasia (AAH) to dysplastic nodule with subfocus of hepatocellular carcinoma or named early hepatocellular carcinoma (eHCC) to small hepatocellular carcinoma (sHCC, diameter<2cm) to obvious typical hepatocellular carcinoma (diameter>2cm). The main purpose of this item is to study whether modalities of imaging effectively characterize different nodules during carcinogenesis and monitor carcinogenesis process and are correlated with cytopathology, molecular abnormal expression.This item focused on: MRI characteristics of different nodules and the abilities of detection and differentiation with various MR scanning and tissue-specific contrast (SPIO) enhanced MRI on induced hepatocellular carcinoma models of cirrhosis rats; dynamic monitoring MRI characteristic of cirrhosis-nodule carcinogenesis on patients with cirrhosis or hepatocellular carcinoma after operation using different MR scanning and enhanced MRI; and comparing cell proliferation (PCNA, Ki-67) and microvessel density (MVD) among normal liver cell, cirrhosis nodule and hepatocellular carcinoma on tissue microarray.The results showed: the induced hepatocellular carcinoma models of cirrhosis rats complied with the multiphase process during carcinogenesis and had different MRI characteristics; SPIO enhanced MRI improved sensitivity of sHCC detection on background of cirrhosis comparing with unenhanced MRI,.32.9% more micro-carcinomas (<1mm) and 12.9% more small carcinomas (1~3mm). During dynamic MRI monitoring of 192 cirrhotic patients, 31 nodules carcinogenesis in 23 patients were determined, and the time of carcinogenesis was 386.90±256.36 days and the carcinoma diameter was 2.2581±1.0736cm. MRI was an effective monitoring tool and the optimized follow-up interval time was 9~12 months. The hyper-expression of PCNA and Ki-67 correlated closely with hyper-proliferation-activity of carcinoma cells. The cirrhosis tissue near carcinomas also showed hyper-proliferation-activity to some degree and indicated possibility of carcinogenesis. MVD expression showed no obvious correlation with PCNA and Ki-67 level and no obviously differentiation among FNH, cirrhosis and HCC, which mean angiogenesis was only a succeeding agent during emergence and development of benign and malignant tumors.

以多种方法MRI及超声监测肝硬化结节的癌变，并作同期的穿刺活检，分析癌变过程中各阶谓峤诘南赴±硇翁峁埂⑾赴鲋郴钚浴⒊裳芑钚浴NA倍体、癌基因N-ras,H-ras c-myc及抑癌基因P53的mRNA表达，探索肝硬化结节癌变的机制及发生发展的规律，总结其相应的MRI特征，划分肝炎后肝硬化高危人群，建立有效可靠的监测序列。