PMID- 30815392
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2235-1795 (Print)
IS  - 1664-5553 (Electronic)
IS  - 1664-5553 (Linking)
VI  - 8
IP  - 1
DP  - 2019 Feb
TI  - Characterization of Hepatocellular Carcinoma Patients with FGF19 Amplification 
      Assessed by Fluorescence in situ Hybridization: A Large Cohort Study.
PG  - 12-23
LID - 10.1159/000488541 [doi]
AB  - BACKGROUND: FGF19 amplification is a relatively novel type of genetic aberration 
      that has been proposed to be a driver of hepatocarcinogenesis. Selective 
      inhibitors of FGFR4, a receptor of FGF19, have been developed as targeted 
      therapies for hepatocellular carcinoma (HCC). Despite the role of FGF19 in 
      mediating HCC progression, the clinicopathological characterization of patients 
      exhibiting FGF19 amplification remains unclear. Immunohistochemical staining is 
      the simplest and most widely used method of identifying aberrations in the FGF19 
      gene, although its specificity is very low. METHODS: This study investigated the 
      prognostic significance of FGF19 amplification in a large cohort of 989 HCC 
      patients using fluorescence in situ hybridization (FISH), which has a high degree 
      of specificity. In addition, FISH data from formalin-fixed, paraffin-embedded 
      sections were compared with copy number variation (CNV) data obtained from fresh 
      frozen sections to validate the use of FISH as a diagnostic tool. RESULTS: FGF19 
      amplifications were detected by FISH in 51 (5.15%) of the 989 patients, and were 
      independently associated with poor survival and a higher risk of tumor 
      recurrence, as well as with poor prognostic factors such as a high alpha-fetoprotein 
      level, hepatitis B or C virus infection, a large tumor size, microvascular 
      invasion, and necrosis. In addition, FGF19 amplification was associated with TP53 
      mutation, and was mutually exclusive with CTNNB1 mutation. The results of the 
      FISH and CNV analyses exhibited a significant concordance rate of 96% (kappa = 0.618, 
      p < 0.001). CONCLUSIONS: These data indicate that FGF19 amplification represents 
      a unique molecular subtype associated with poor prognostic characteristics, which 
      supports the hypothesis that the FGF19-FGFR4 signaling pathway plays an important 
      role in hepatocarcinogenesis. We have also demonstrated that FISH is a viable 
      alternative to CNV analysis, offering a number of advantages in the clinical 
      setting.
FAU - Kang, Hyo Jeong
AU  - Kang HJ
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Haq, Farhan
AU  - Haq F
AD  - Department of Biosciences, COMSATS Institute of Information and Technology, 
      Islamabad, Pakistan.
FAU - Sung, Chang Ohk
AU  - Sung CO
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Choi, Jene
AU  - Choi J
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Hong, Seung-Mo
AU  - Hong SM
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Eo, Soo-Heang
AU  - Eo SH
AD  - Department of Statistics, Korea University, Seoul, Republic of Korea.
FAU - Jeong, Hui Jeong
AU  - Jeong HJ
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Shin, Jinho
AU  - Shin J
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Shim, Ju Hyun
AU  - Shim JH
AD  - Department of Gastroenterology, Asan Liver Center, Asan Medical Center, 
      University of Ulsan College of Medicine, Seoul, Republic of Korea.
FAU - Lee, Han Chu
AU  - Lee HC
AD  - Department of Gastroenterology, Asan Liver Center, Asan Medical Center, 
      University of Ulsan College of Medicine, Seoul, Republic of Korea.
FAU - An, Jihyun
AU  - An J
AD  - Department of Gastroenterology, Asan Liver Center, Asan Medical Center, 
      University of Ulsan College of Medicine, Seoul, Republic of Korea.
FAU - Kim, Mi-Ju
AU  - Kim MJ
AD  - Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan 
      College of Medicine, Seoul, Republic of Korea.
FAU - Kim, Kyu-Pyo
AU  - Kim KP
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
FAU - Ahn, Sung-Min
AU  - Ahn SM
AD  - Department of Hematology-Oncology, Gachon Institute of Genome Medicine and 
      Science, Gachon University Gil Medical Center, Incheon, Republic of Korea.
FAU - Yu, Eunsil
AU  - Yu E
AD  - Department of Pathology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20180522
PL  - Switzerland
TA  - Liver Cancer
JT  - Liver cancer
JID - 101597993
PMC - PMC6388559
OTO - NOTNLM
OT  - FGF19
OT  - Fluorescence in situ hybridization
OT  - Hepatocellular carcinoma
OT  - High copy number amplification
OT  - Prognosis
EDAT- 2019/03/01 06:00
MHDA- 2019/03/01 06:01
PMCR- 2020/02/01
CRDT- 2019/03/01 06:00
PHST- 2018/01/08 00:00 [received]
PHST- 2018/03/18 00:00 [revised]
PHST- 2019/03/01 06:00 [entrez]
PHST- 2019/03/01 06:00 [pubmed]
PHST- 2019/03/01 06:01 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - lic-0008-0012 [pii]
AID - 10.1159/000488541 [doi]
PST - ppublish
SO  - Liver Cancer. 2019 Feb;8(1):12-23. doi: 10.1159/000488541. Epub 2018 May 22.