Study of Genomic Heterogeneity of Hepatocellular Carcinomas by Using Arbitrary Primer Polymerase Chain Reaction (AP-PCR)
Seong Ho Kim, M.D., Seong Woo Hong, M.D., Jeong Hyun Kim, Ph.D.1, Yun Kyung Kang, M.D.2, Tae Gil Heo, M.D., Yeo Goo Chang, M.D., In Wook Paik, M.D. and Hyucksang Lee, M.D.
Department of Surgery, 1Institute of Molecular Biology, 2Department of Pathology, Seoul Paik Hospital, Inje University, Seoul, Korea Background/Aims: Discrimination between intrahepatic me- tastasis (IM) and de novo multicentric occurrence (MO) in multiple hepatocellular carcinoma (HCC) is important not only for the study of hepatocarcinogenesis but also for deter- mination of therapeutic strategies. The purpose of this study is to evaluate the clonality of multiple or recurrent hepato- celluar carcinoma by using AP-PCR.
Methods: Paraffin-embedded blocks of 9 multiple synchro- nous hepatocellular carcinomas, one recurrent hepatocellular carcinoma and one combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma were used. None of the tumors
was larger than 3.3 cm in diameter. Microdissection was done by using sterile 27 gauge needles and microscope. Two different arbitrary primers (AR3, ZF3) were utilized in AP- PCR. The clonality of tumor was assessed by DNA band pattern (DNA fingerprint) of PCR product.
Results: Eight of nine multiple synchronous hepatocellular carcinomas had distinctly different DNA fingerprints. One recurrent hepatocellular carcinoma and one combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma also had different DNA fingerprints.
Conclusion: AP-PCR is a simple and very powerful method for determining the clonality of multiple hepatocellular carci- nomas. The majority of multiple, small-sized hepatocellular carcinomas have different clonalities and it seems that a significant number of multiple hepatocellular carcinomas are of multicentric, de novo nature. (Korean J HBP Surg 2002;
6:26-32)
Key Words: Hepatocellular carcinoma, Intrahepatic metasta- sis, Multicentric occurrence, Clonality, AP-PCR, DNA fingerprinting
: , , , Clonality,
, DNA
