[1596] Epidermal Growth Factor Receptor and Glypican-3 in Hepatocellular Nodules: A Clinicopathologic Study

LE Kernochan, J Alexander, PE Swanson, MM Yeh. Univ. of Washington, Seattle

Background: Epidermal growth factor receptor (EGFR) is overexpressed in hepatocellular carcinoma (HCC) and is a potential therapeutic target, but correlation between EGFR and clinicopathologic attributes of HCC including clinical outcome is controversial and correlation between EGFR and the novel HCC selective marker Glypican-3 (GP3) is lacking. We herein examined the expression of these markers in HCC and other diagnostically challenging, mimicking lesions including high grade dysplastic nodule (HGDN) and hepatocytic adenoma (HCA), and the correlation between GP3 and EGFR in HCC with correlation to survival.
Design: Formalin-fixed sections of 59 HCC, 8 HGDN, and 17 HCA were stained with antibodies to EGFR and GP3. The results were scored for intensity (none, weak, moderate, strong) and distribution (none, <10%, 10-33%, 34-66%, 67-100%) in lesional and non-lesional cells. The results were compared with differentiation (well, moderate or poor), Edmonson-Steiner (ES) nuclear grade (1-4) and survival in HCC.
Results: GP3 and EGFR were very sensitive for HCC, but GP3 was more specific in separating HCC from cirrhotic liver, HGDN, and HCA:

Sensitivity/Specificity of GP3 and EGFR in distinguishing HCC from cirrhotic liver, HGDN, and HCA

	cirrhotic liver	HGDN	HCA
GP3	85.7/100	85.7/50	85.7/100
EGFR	82.5/54.2	82.5/16.7	n/a

Neither EGFR nor GP3 staining correlated with survival. Poorer differentiation of HCC was associated with greater GP3 intensity (p=0.01) and distribution (p=0.0007). Higher ES grade also correlated with higher GP3 intensity (p<0.0001) and distribution (p=0.0007). Although there was significant correlation between EGFR and GP3 in both intensity (p=0.01) and distribution (p=0.005), EGFR intensity and distribution alone did not correlate with HCC differentiation or ES grade.
Conclusions: To our knowledge, this is the first study investigating both the expression of EGFR and GP3 in HCC and their correlation, and to correlate with clinical outcome. GP3 is a sensitive and specific marker for HCC that readily distinguishes HCC from cirrhotic liver and HCA. Intensity and distribution of GP3 staining correlate with poorer differentiation and higher ES grade. Our results of significant correlation between EGFR and GP3 staining in HCC, but no correlation in survival based on staining characteristics further support the recent phase 2 trial results that there has not been a survival difference based on EGFR status. The role for GP3 in the EGFR hepatocarcinogenesis pathway awaits further investigation.
Category: Liver & Pancreas

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 227, Tuesday Morning