High mobility group A1 is expressed in metastatic adenocarcinoma to the liver and intrahepatic cholangiocarcinoma, but not in hepatocellular carcinoma: its potential use in the diagnosis of liver neoplasms.

Abstract

An increased level of high mobility group A (HMGA) gene/protein expression has been demonstrated to be associated with many human neoplasms originating from a variety of tissues. However, HMGA1 expression has not yet been studied in hepatic tumors. In this study, we analyzed HMGA1 expression in hepatic primary and metastatic tumors in order to verify whether determination of the HMGA1 expression level could provide any diagnostic advantages in the pathological diagnosis of hepatic tumors. Twenty samples of hepatocellular carcinoma, 5 samples of intrahepatic cholangiocarcinoma, and 21 samples of metastatic adenocarcinoma to the liver (15 metastatic tumors from colorectal carcinoma and 6 metastatic tumors from pancreatic carcinoma) were analyzed immunohistochemically using an HMGA1-specific antibody. While no significant nuclear immunoreactivity was found in hepatocytes of non-neoplastic liver tissue, 40% (2/5) of intrahepatic cholangiocarcinomas, 53.3% (8/15) of metastatic lesions from colorectal carcinoma, and 100% (6/6) of metastatic lesions from pancreatic carcinoma showed positive immunoreactivity. In contrast, all 20 samples of hepatocellular carcinoma were negative for HMGA1 nuclear immunoreactivity. Thus, hepatocellular carcinoma represents the first case of malignant neoplasia in which HMGA1 expression is not induced, which presents a striking contrast to several previous studies demonstrating the significance of increased HMGA gene/protein levels in carcinogenesis and/or tumor progression. Based on these findings, we conclude that the HMGA1 protein level could serve as a potential diagnostic marker that may enable the differential diagnosis between hepatocellular carcinoma and intrahepatic cholangiocarcinoma or metastatic adenocarcinoma to the liver.