[1753] Utility of HSP70, Glutamine Synthethase and Glypican-3 in Distinguishing Hepatocellular Adenoma from Well-Differentiated Hepatocellular Carcinoma

Thuy B Nguyen, Sanjay Kakar. University of California, San Francisco, CA

Background: Well-differentiated hepatocellular carcinoma (WD-HCC) can mimic high-grade dysplastic nodule (HGDN) in cirrhotic liver and hepatocellular adenoma (HA) in non-cirrhotic liver. Combined use of heat shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 (GPC) has been shown to help in distinguishing HGDN from HCC. This study evaluates the efficacy of this panel in distinguishing HA from WD-HCC.
Design: Immunohistochemistry for HSP70, GS and GPC was done in typical HA (n=24), HGDN (n=16), adenoma-like HCC (n=7) and WD-HCC (n=41;19 non-cirrhotic, 22 cirrhotic). Adenoma-like HCCs were tumors that resembled HA, but in which a diagnosis of HCC was based on focal atypical morphological features like small cell change, cytologic atypia, prominent pseudoacini and/or reticulin loss. The staining intensity was graded from 0-3. GS was considered positive if 2+ or 3+ staining was observed in ≥50% of tumor cells. GPC and HSP70 were scored positive if 2+ or 3+ staining was seen in ≥25% of tumor cells.
Results: Expression of HSP70, GS and GPC was seen more commonly in WD-HCCs than typical HAs and DNs. Expression in WD-HCC and adenoma-like HCC was similar. The overall sensitivity was highest with HSP70, which stained nearly two-thirds of WD-HCC, while GS and GPC were positive in one-third of cases. Positivity for ≥2 markers was seen in 17(41%) WD-HCCs and 3(43%) adenoma-like HCCs; this was rare in DN (1/16) and not seen in typical HA.

	HSP70	GPC	GS	HSP70+GPC	HSP70+GS	GPC+GS	HSP70+GPC+GS
HA, typical (n=24)	3 (13%)	0 (0%)	1 (7%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Adenoma-like HCC (n=7)	4 (57%)	1 (14%)	3 (43%)	1 (14%)	3 (43%)	1 (14%)	1 (14%)
DN (n=16)	3 (19%)	1 (6%)	2 (13%)	1 (6%)	1 (6%)	1 (6%)	1 (6%)
WD-HCC (n=41)	25 (61%)	13 (32%)	15 (37%)	11 (27%)	11 (27%)	7 (17%)	6 (15%)
p value*	0.007	0.001	0.002	0.004	0.004	0.032	0.054

*typical HA vs. WD-HCC


Conclusions: HSP70, GS and GPC are expressed significantly more often in WD-HCC than typical HA and HGDN, but the overall sensitivity of these markers is not high. Positivity for ≥2 of these markers was not observed in typical HA and strongly supports HCC, although less than half of WD-HCC were positive for ≥2 markers. The staining pattern of adenoma-like HCC closely resembled WD-HCC. Since these tumors are most likely to be confused with typical HA, this combination of stains is likely to be useful in clinical practice.
Category: Liver

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 250, Tuesday Morning