Utility of an immunohistochemical panel consisting of glypican-3, heat-shock protein-70, and glutamine synthetase in the distinction of low-grade hepatocellular carcinoma from hepatocellular adenoma.
BACKGROUND
The pathologic distinction between hepatocellular carcinoma (HCC) and hepatocellular adenoma (HCA) is sometimes problematic due to histologic overlap between the 2 entities, a problem amplified on small biopsy specimens. Several recently characterized immunohistochemical markers such as glypican-3 (GPC-3), heat-shock protein-70 (HSP-70), and glutamine synthetase (GS) help distinguish dysplastic nodules from HCC. The utility of this panel in the distinction of low-grade hepatocellular carcinoma (LG-HCC) from HCA has not been fully described.


OBJECTIVE
To determine whether the above markers are useful in the distinction of HCCs from HCAs.


METHODS
Tissue microarrays were constructed with 30 LG-HCCs and 18 HCAs. The arrays were stained with the above markers and analyzed with respect to amount and pattern of staining. GPC-3 and HSP-70 were considered positive when 10% of tumor cells showed immunoreactivity. GS was considered positive when 50% of tumor cells showed immunoreactivity.


RESULTS
GPC-3 was positive in 13 of 30 LG-HCCs and 0 of 18 adenomas. The sensitivity was 43% and the specificity was 100%. HSP-70 was positive in 14 of 30 LG-HCCs and 0 of 18 adenomas. The sensitivity was 46% and the specificity was 100%. GS was positive in 24 of 30 LG-HCCs and 9 of 18 adenomas. The sensitivity was 80% and the specificity was 50%.


CONCLUSIONS
GPC-3 and HSP-70 are helpful in separating carcinomas from adenomas. GS is not useful in this clinical context.
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA. smL2179@columbia.edu
Stephen M
SM
Lagana
Marcela
M
Salomao
Fei
F
Bao
Roger K
RK
Moreira
Jay H
JH
Lefkowitch
Helen E
HE
Remotti
D018248:Adenoma, Liver Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D005974:Glutamate-Ammonia Ligase / Q000235:genetics* / Q000378:metabolism; D053673:Glypicans / Q000235:genetics* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D018840:HSP70 Heat-Shock Proteins; D005974:Glutamate-Ammonia Ligase