[1554] A Comparison of the Immunophenotype of Hepatocellular Carcinoma and Non-Lesional Hepatocytes When Analyzed with Next-Generation Markers.

Stephen M Lagana, Marcela Salamao, Fei Bao, Roger K Moreira, Jay H Lefkowitch, Helen Remotti. Columbia University Medical Center, New York, NY

Background: Many novel immunohistochemical stains have recently been introduced to help distinguish hepatocellular carcinomas (HCC) from non-malignant hepatocytes. Among these are Glypican-3 (GPC-3), heat shock protein 70 (HSP-70), and glutamine synthetase (GS). The role of Glucose-transporter-1 (GLUT-1) has been controversial in HCC. In addition, a recent study demonstrated Arginase-1 (Arg-1) to be a more sensitive and specific marker of hepatocellular differentiation than hepatocyte paraffin antigen (HepPar1) in HCC. We undertook a comparative study of these markers in HCC and non-lesional hepatocytes.
Design: Tissue microarrays were constructed from 47 cases (17 high grade, 30 low grade) including both HCC and non-lesional (mostly cirrhotic) liver. Staining was performed for the above markers. A cut-off of 5% was set for positivity.
Results:

Results

		HSP-70	GPC-3	GS	GLUT-1	Hep-Par1	Arg-1
Sensitivity (%)	High grade (17)	53	65	94	6	88	100
	Low grade (30)	47	50	93	0	87	97
Average percentage of cells staining in positive cases	High grade	49	49	72	5	72	90
	Low grade	57	55	74	0	78	91

Conclusions: HSP-70 and GPC-3 are helpful in distinguishing malignant from benign hepatocytes when positive, but suffer from low sensitivity in small specimens. Neither stained non-lesional tissue (100% specificity). GS suffers from lack of specificity as it normally stains benign hepatocytes. Though the pattern in benign tissue is different from that of HCC, this can be difficult to appreciate on small biopsies of cirrhotic liver. However, since GS sensitivity is high, when negative it is helpful in excluding a hepatocellular origin. GLUT-1 immunohistochemistry is non-contributory in HCC. In our cases, Arginase-1 was superior to Hep-Par1, with positive staining in all but one HCC and, importantly, in all cases of Hep-Par1 negative HCC. Hep-Par1 was positive in the only Arginase-1 negative HCC, thus both should be considered together when the index of suspicion is high for a tumor of hepatocellular origin.
Category: Liver & Pancreas

Tuesday, March 1, 2011 2:15 PM

Platform Session: Section C, Tuesday Afternoon