Loss of heterozygosity and microsatellite instability in human non-neoplastic hepatic lesions

Aims/background: Carcinogenesis is thought to be a multistage process that occurs as a result of mutations in oncogenes and tumor suppressor genes. On e way to monitor a vast range of these changes is by microsatellite PCR amp lification that detects loss of heterozygosity and microsatellite instabili ty between normal and tumor specimens of the same subject. Viral cirrhosis is considered a strong predisposing factor for the development of liver can cer. The aim of the study therefore was to examine precancerous hepatic les ions and compare them with others not considered as high risk for hepatocel lular carcinoma. Methods: We examined 43 subjects for 19 microsatellite mar kers spanning chromosomes 1, 9 and 17. Normal specimens were blood samples that were compared to liver needle biopsies. Samples were classified accord ing to histological features as non-cancerous (10 cases) and pre-cancerous (33 cases, chronic hepatitis and cirrhosis). Results: Our results indicate that there is a tendency of increased chromosomal alteration as lesions bec ome chronic. Samples from patients with antibodies to antibodies for hepati tis C virus show more alterations than hepatitis B positive samples. Steato hepatitis, a disease of unknown etiology, appears to have a high number of microsatellite abnormalities. Conclusions: Microsatellite APOA2 located on chromosome 1, shows a statistically significant increase in the rate of los s of heterozygosity as liver lesions become more severe, indicating the pre sence of tumor suppressor genes which may be involved in the development of these lesions.