[1589] Insulin-Like Growth Factor 1 Receptor Beta (IGF-1R Beta) Expression in Hepatocellular Carcinoma (HCC)

W Jiang, X Liu, F Aucejo, R Kim, LM Yerian. Cleveland Clinic, Cleveland, OH

Background: The IGF signaling axis, including IGF-I and IGF-II and their receptor IGF-1R, has been implicated in development and progression of HCC. Constitutive activation of IGF-1R is frequently observed in HCC cell lines and is crucial for oncogenic transformation and tumor cell survival. However, IGF-1R expression by immunohistochemistry and its significance in human HCC have not been reported.
Design: 126 patients with HCC underwent liver transplant from 06/2002 to 08/2006. 72 paired HCC and corresponding adjacent cirrhotic liver samples were studied. Immunohistochemical staining for IGF-1R beta was performed on formalin-fixed, paraffin-embedded sections. IGF-1R beta immunoreactivity was scored using a four-tier grading system (0 to 3+). Correlation of IGF-1R beta staining and clinicopathologic features of HCC including tumor grade, being beyond Milan criteria, vascular invasion, and underlying liver disease was determined.
Results: 58.3% (42/72) of HCC expressed IGF-1R beta, whereas only 5.6% (4/72) of non-tumorous livers showed IGF-1R beta expression in (p<0.0001). Please see tables 1 and 2 for the correlation of IGF-1R with various clinicopathologic features.

Table 1. IGF-1R beta correlation with tumor variables

IGF-1R beta in tumor	Vascular invasion	Beyond Milan Criteria	Poor tumor grade	Recurrence
Positive (0.5-3) (n=42)	13 (31.0%)	25 (40.7%)	12 (28.6%)	3 (7.1%)
Negative (0) (n=30)	5 (20%)	25 (16.5%)	1 (3.3%)	1 (3.3%)
P value	0.269	0.030	0.010	0.635

Table 2. IGF-1R beta correlation with etiology

IGF-1R beta in tumor	HCV	HBV	Alcohol	NASH
Positive (0.5 - 3) (n=42)	29 (69.0%)	2 (4.8%)	10 (23.8%)	1 (2.4%)
Negative (0) (n=30)	17 (56.7%)	3 (10.0%)	5 (16.7%)	6 (20.0%)
P value	0.325	0.643	0.562	0.018

Conclusions: Our results show that HCC have a higher expression of IGF-1R beta than adjacent non-tumorous cirrhotic liver. IGF-1R beta expression is associated with poor tumor differentiation and tumors beyond Milan criteria. Interestingly, IGF-1R expression is less frequent in non-alcoholic steatohepatitis (NASH)-associated HCC than in other causes of cirrhosis. Our findings support a role for IGF-1R signaling in HCC tumorigenesis and strongly suggest an intrinsic difference in IGF-1R signaling in HCC occurring in NASH versus other liver diseases.
Category: Liver & Pancreas

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 230, Tuesday Morning