Hepatic angiomyolipoma and hepatic stellate cells share a similar gene expression profile.
OBJECTIVE
Angiomyolipomas (AMLs) of the liver are rare neoplasms composed of large epithelioid cells with intermixed fat and blood vessels. Hepatic AMLs have no clear normal-cell counterpart in the liver. However, AMLs and stellate cells both are positive for neural crest-derived markers including HMB-45 antigen.


METHODS
To further explore the similarities between hepatic AMLs and stellate cells, gene expression of a hepatic AML was studied by cDNA microarray. Real-time polymerase chain reaction was used to confirm gene expression. Hepatic stellate cells can be quiescent, activated, or have a myofibroblastic phenotype depending on their state of activation. Expression of known markers of activated stellate cells was compared between the AML, activated primary mouse stellate cells, and stellate cell lines with activated and myofibroblastic phenotypes. Next, 5 novel genes from the AML were selected because they were not previously known to be markers of stellate cells and mRNA expression measured in the activated mouse stellate cells and in myofibroblastic stellate cell lines. Finally, expression levels of 10 novel genes were determined in 5 cirrhotic and 5 noncirrhotic human livers.


RESULTS
Overexpression of known markers of activated stellate cells including transforming growth factor beta (TGF- beta ), smooth muscle actin, and collagen was found in the hepatic AML. Three of 5 novel markers that were identified in the AML, RRAD (Ras-related associated with diabetes), CTSK (cathepsin K), and NIBAN were also found to be overexpressed in activated stellate cells compared with quiescent or myofibroblastic stellate cells. In addition, 9 of 10 novel genes overexpressed in AML were also overexpressed in cirrhotic human livers versus noncirrhotic livers.


CONCLUSIONS
Hepatic AMLs share a similar gene expression profile and may differentiate toward activated stellate cells.
Kannangai
Rajesh
R
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Diehl
Anna Mae
AM
Sicklick
Jason
J
Rojkind
Marcus
M
Thomas
David
D
Torbenson
Michael
M
D018207:Angiomyolipoma / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm; D015415:Biomarkers / Q000032:analysis; D002460:Cell Line; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
D000951:Antigens, Neoplasm; D015415:Biomarkers; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins