Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma

• Published in: Yonsei medical journal Vol. 62; no. 7; pp. 622 - 630
• Main Authors: Kim, Honsoul, Choi, Junjeong, Yu, Dae-Yeul, Choi, Hye Jin
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.07.2021; 연세대학교의과대학
• Subjects: Animals; Carcinoma, Hepatocellular - diagnostic imaging; Carcinoma, Hepatocellular - genetics; Contrast Media; Gadolinium DTPA; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - genetics; Magnetic Resonance Imaging; Mice; Mice, Transgenic; Organic Anion Transporters; Original; Peptides; Retrospective Studies; 의학일반; Carcinoma, hepatocellular; magnetic resonance imaging; gadolinium ethoxybenzyl DTPA
• ISSN: 0513-5796; 1976-2437; 1976-2437
• DOI: 10.3349/ymj.2021.62.7.622

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. 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. 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 high-grade 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 ( =0.004). Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acid-enhanced MRI in moderately differentiated HCC.