Identification Of Preneoplastic Nodules Of Altered Hepatocytes In Cirrhotic Livers, With Respect To Their Genetic Alterations

Progression of hepatocellular carcinoma (HCC) is a stepwise process that proceeds from pre-neoplastic lesions to advanced HCC. Foci/nodules of altered hepatocytes (FAH/NAH) have been demonstrated to represent preneoplastic lesions in hepatocarcinogenesis. But the molecular changes associated with this progression are unclear. To understand the multistep process of hepatocarcinogenesis at the molecular level and the relationship between FAH/NAH and HCC, We compared loss of heterozygosity (LOH) of 28 microsatellite site between 17 FAH/NAH,33 FAH/NAH with small cell change (SCC) and 50 HCC. LOH was found at least one microsatellite site LOH in 14 FAH/NAH(82%), and the mean was 2.28 (0-6); LOH was found at least one microsatellite site LOH in 28 FAH/NAH with SCC (82%) of total 33, and the mean was 3.18(0-8); and in 22 HCC,19 HCC(86%) showed LOH, and the mean was 5.42 (0-12). This data supported NAH was moloclonality proliferation whether with SCC or not, and foci/nodules of altered hepatocytes (FAH/NAH) was real preneoplastic lesions in hepatocarcinogenesis, was intraepithelial neoplasia.FAH/NAH--> FAH/NAH with SCC-->HCC progression, there were some special LOH changes in every stage, and was related with carcinogenesis in early stage, tumor development and progression respectively.At the same time, we detected several protein expression which may be related with the LOH in chromosome by immunohistochemistry (IHC), and found WWOX may be associated with LOH in 16q and with early carcinogenesis in hepatocellular carcinoma.