Poster Session 3: Basic Hepatobiliary Neoplasia
Authors: Jennifer Au, Angel Dago, Kelly Bethel, Peter Kuhn, Ran- Dolph Schaffer, Randolph Schaffer, Arihiro Aihara, Chiung-Kuei Huang, Mark Olsen, Qiushi Lin, Waihong Chung, Qi Tang, Xiaoqun Dong, Jack Wands, Marie-Christine Guilbert, Geneviève Soucy, Dominique Trudel, Bich Nguyen, Poh Tan, Anu Venkatesh, Stephen Ward, Claudia Canasto-Chibuque, Anna Koh, Venugopalan Nair, Manjeet Deshmukh, Shigeki Nakagawa, Xiaochen Sun, Masahiro Kobayashi, Hiromitsu Kumada, Yujin Hoshida, Hiromi Kan, Hideyuki Hyogo, Hiroshi Aikata, Tomoki Kobayashi, Takayuki Fukuhara, Noriaki Naeshiro, Yohji Honda, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Takeshi Aiyama, Tatsuya Orimo, Hideki Yokoo, Takanori Ohata, Kanako Hatanaka, Yutaka Hatanaka, Yoshihiro Matsuno, Kenji Wakayama, Tatsuhiko Kakisaka, Yosuke Tsuruga, Hirofumi Kamachi, Toshiya Kamiyama, Akinobu Take- Tomi, Changjae Hur, Byoung Jang, Jeong Kim, Kyung Yang, Hye Park, Sang Lee, Eun Choi, Jung Lee, Jin Woo, Jaeseok Hwang, Yoo Kang, Koo Kang
Journal: Hepatology (2014)

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide.Over 600,000 new cases are diagnosed each year.Early stage disease can be cured with surgical resection or liver transplantation.Liver transplantation offers the best chance at a cure; however, recurrence rates are as high as 40% for those transplanted.The enumeration of circulating tumor cells (CTCs) is an independent prognostic biomarker in patients with malignancies including breast and colon cancer.CTCs in the peripheral blood of HCC patients have been correlated to tumor size, portal vein tumor thrombosis, and stage.There is no data regarding the utility of CTC identification and molecular characterization to predict patients at high risk of HCC recurrence.Copy number variations (CNVs) are a mechanism of genetic mutation through which malignancy can arise.PUR-POSE: The purpose of our study is to assess CNV profiles of CTCs and matched primary tumor samples as biomarkers for malignant potential and risk of HCC recurrence.METHODS: Serum and tumor samples were collected from 100 patients over three years.Peripheral blood samples collected before, at the time of, and at multiple points after surgery were analyzed for CTCs.CTCs isolated from the peripheral blood were identified using a high definition CTC assay and primary tumor tissues were sampled as touch preps.The genomes of the isolated CTC and touch prep single cells were amplified and sequenced to determine genome wide CNV profiles (single cell genomic analysis).RESULTS: Presently, 45 patients have undergone total hepatectomy with liver transplantation and 16 partial hepatic resections for HCC with 3 episodes of recurrence to date.One patient recurred after partial hepatectomy and two after transplant.CTC levels varied between patients and at different times in the clinical course.Over 80% of CTCs and primary tumor cells identified were successfully isolated, and genetically amplified for CNV profiling.CNV profiles of different cell populations from the same patient often had similar mutation patterns.Some of those mutations identified have been associated with more aggressive malignancy.CONCLU-SION: We successfully demonstrated the ability to perform high-content CNV analysis of single cells from primary HCC tumors and CTCs in patients with tumor recurrence following definitive surgical therapy.The initial success of this pilot study suggests that CNV analysis of CTCs may prove beneficial in predicting risk of HCC recurrence after liver transplantation or resection.A comprehensive study to further investigate is currently underway.