Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma
	    		
		   		
		   			
		   		
	    	
    	 
    	10.3349/ymj.2021.62.7.622
   		
        
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Honsoul KIM
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Junjeong CHOI
			        		
			        		;
		        		
		        		
		        		
			        		Dae-Yeul YU
			        		
			        		;
		        		
		        		
		        		
			        		Hye Jin CHOI
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
			        		
		        		
	        		
        		 
        	
        	
        	
        		- Publication Type:Original Article
 
        	
        	
            
            
            	- From:Yonsei Medical Journal
	            		
	            		 2021;62(7):622-630
	            	
            	
 
            
            
            	- CountryRepublic of Korea
 
            
            
            	- Language:English
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	Purpose:Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. 
				        	
				        
				        	Materials and Methods:Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. 
				        	
				        
				        	Results:We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with highgrade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). 
				        	
				        
				        	Conclusion:Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acidenhanced MRI in moderately differentiated HCC.