The Effect of the Etiology of Cirrhosis on Glypican-3 Expression in Hepatocellular Carcinoma
Jared M Orrock, Taofic Mounajjed, Lizhi Zhang, Tsung-Teh Wu. Mayo Clinic, Rochester, MN
Background: Overexpression of Glypican-3 (GPC3), a cell membrane bound proteoglycan which modulates hepatocyte growth and differentiation, occurs frequently in hepatocellular carcinoma (HCC); an immunhistochemical stain for GPC3 is a useful adjunct in the diagnosis of HCC. Most HCCs occur in cirrhotic livers, but how the etiology of cirrhosis affects GPC3 expression in HCC has not been studied in detail. Because chronic hepatitis C (HCV) and steatohepatitis are the most common causes of cirrhosis, we aim to compare GPC3 expression between HCC arising in cirrhosis due to chronic hepatitis C (HCV) and HCC arising in cirrhosis due to steatohepatitis.
Design: The immunohistochemical expression of GPC3 in 60 patients with HCC occurring in explanted livers with HCV (n=30) and steatohepatitis (30; 10 alcoholic, and 20 non-alcoholic) related cirrhosis was examined. HCC was graded using WHO classification criteria (G1: well differentiated, G2: moderately differentiated, and G3: poorly differentiated). All tumors were scored for cytoplasmic and membranous staining. A tumor was considered positive for GPC3 if >10% of the neoplastic cells showed cytoplasmic and membranous immunoreactivity. The expression of GPC3 in HCC was correlated to clinicopathologic features, including etiology of cirrhosis, tumor differentiation, and focality of tumor.
Results: There was no difference of tumor differentiation between HCV associated HCC (6 G1, 18 G2, and 6 G3) and steatohepatitis associated HCC (5 G1, 17 G2 and 8 G3), p= 0.82. GPC3 expression occurred significantly more frequently in HCV associated HCC (83%, 25 of 30) compared to steatohepatitis associated HCC (50%, 15 of 30), p= 0.01. In HCV related HCC, 83% of G1, G2 and G3 tumors were positive for GPC3. In steatohepatitis related HCC, 60% of G1, 36% of G2, and 63% of G3 tumors were positive for GPC3. In both groups, GPC3 expression showed no correlation with tumor differentiation. Etiology of steatohepatitis (alcoholic vs non alcoholic) did not correlate with GPC3 expression, p= 0.14. Multifocal HCC occurred in 66 % (20 of 30) of HCC associated with HCV and in 50% (15 of 30) of HCC associated with steatohepatitis and did not correlate with GPC3 expression, p= 0.055.
Conclusions: HCC arising in cirrhosis due to HCV is more likely to express GPC3 than HCC arising in cirrhosis due to steatohepatitis. Hence, the significance of GPC3 immunostain results in hepatic tumors should be interpreted in light of the patient's underlying liver disease. The etiology of this difference is unknown but GPC3 activation may have a role in HCV induced carcinogenesis.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 243, Tuesday Morning