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Caveolin and thrombospondin expression during hepatocellular carcinogenesis
Lisa M Yerian1, Robert A Anders, Maria Tretiakova
1Department of Pathology, University of Chicago Hospitals, Chicago, IL 60637, USA.
The American Journal of Surgical Pathology
|April 24, 2004
Summary
Macroregenerative and dysplastic nodules (MDNs), precursors to liver cancer, show altered caveolin-1 and thrombospondin-1 expression, primarily in vascular cells, not hepatocytes. This suggests changes in blood supply, not direct malignant transformation, influence these gene profiles.
Area of Science:
- Hepatology
- Vascular Biology
- Oncogenesis
Background:
- Macroregenerative and dysplastic nodules (MDNs) are recognized precursors to hepatocellular carcinoma (HCC).
- Previous microarray studies indicated aberrant expression of caveolin-1 and thrombospondin-1 in MDNs.
- These genes are implicated in tumorigenesis in other cancer types.
Purpose of the Study:
- To investigate the cellular localization and expression patterns of caveolin-1 and thrombospondin-1 in MDNs.
- To determine if altered gene expression in MDNs is associated with hepatocytes or the tumor vasculature.
- To clarify the role of these genes in the progression from MDN to HCC.
Main Methods:
- Immunohistochemistry was employed to detect caveolin and thrombospondin expression.
- Analysis included 14 MDNs from hepatitis C cirrhotic livers and tissue arrays of MDNs, HCC, and nonneoplastic liver.
- Expression levels were compared between MDNs, HCC, and adjacent cirrhotic liver tissues.
Main Results:
- Hepatocytes were consistently negative for caveolin; sinusoidal endothelial cells showed increased caveolin expression in MDNs (78%) compared to cirrhotic liver.
- Caveolin expression was not significantly increased in most HCCs (26%) versus nonneoplastic liver.
- Thrombospondin staining was weak/negative in hepatocytes of MDNs (84%) and HCCs (94%), but present in the vasculature of MDNs and hepatic arteries.
Conclusions:
- Aberrant caveolin-1 and thrombospondin-1 expression in MDNs is primarily localized to vascular components, not hepatocytes.
- These altered expression profiles likely reflect changes in the vascular supply to MDNs rather than direct hepatocyte malignant transformation.
- Histologic techniques are crucial for accurate interpretation of gene expression data from microarray analyses.