Abnormal expression of insulin-like growth factor-II and its dynamic quantitative analysis at different stages of hepatocellular carcinoma development.

Background: Hepatocellular carcinoma (HCC) is characterized by multiple causes, clear multiple stages and a multifocal process of tumor progression related intimately to the overexpression of many cellular factors. The aim of this study was to investigate the dynamic expression of insulin-like growth factor-II (IGF-II) and its abnormal alteration in the early stages of HCC development.

Methods: Hepatoma models were induced by 2-fluorenylacetamide (2-FAA) in male Sprague-Dawley rats. Morphological changes of rat livers were assessed by pathological examination (HE staining). The levels of IGF-II expression in the livers and sera of rats were quantitatively detected by an enzyme-linked immunosorbent assay (ELISA). Simultaneously, the expression and cellular distribution of liver IGF-II were analyzed by immunohistochemistry.

Results: Histological examination confirmed that rat hepatocytes showed changes from granule-like degeneration to atypical hyperplasia to HCC, and progressively increasing hepatic IGF-II levels during HCC development. The levels of hepatic or serum IGF-II in HCC tissues and sera were significantly higher than those in normals and rats with degeneration. The immunohistochemical evidence indicated the positive expression and hepatocyte distribution of IGF-II in rat hepatoma. A positive relationship of IGF-II levels was found between liver tissues and sera of experimental rats (P<0.01).

Conclusion: Hepatic IGF-II may participate in hepatocyte cancer development and detection of IGF-II expression during HCC development could be a useful molecular marker for its early diagnosis.