title: Fibroblast growth factor receptor isotype expression and its association with overall survival in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications.
  
  
  METHODS
  Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis.
  
  
  RESULTS
  FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set.
  
  
  CONCLUSIONS
  FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.
authors.affiliation: Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kang Mo
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Yu
authors.affiliation: Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Innovative Cancer Research, Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Seung-Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Han Chu
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yung Sang
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor
keywords: Fibroblast growth factor; Hepatocellular carcinoma; Immunohistochemistry; Receptor; Survival
references.citation: J Biol Chem. 1999 May 28;274(22):15947-52
references.pmid: 10336501
references.citation: Mol Carcinog. 2009 Jun;48(6):553-62
references.pmid: 19009564
references.citation: Semin Liver Dis. 2010 Feb;30(1):3-16
references.pmid: 20175029
references.citation: Am J Pathol. 2010 Mar;176(3):1433-42
references.pmid: 20093481
references.citation: Oncology. 2010;78(5-6):361-8
references.pmid: 20798558
references.citation: J Biol Chem. 2010 Sep 24;285(39):30069-78
references.pmid: 20657013
references.citation: Hepatology. 2011 Mar;53(3):854-64
references.pmid: 21319186
references.citation: PLoS One. 2011;6(5):e19618
references.pmid: 21573021
references.citation: BMC Cancer. 2012;12:56
references.pmid: 22309595
references.citation: Eur J Surg Oncol. 2012 Apr;38(4):286-95
references.pmid: 22281155
references.citation: Surgery. 2012 May;151(5):700-9
references.pmid: 22284764
references.citation: Biochem Biophys Res Commun. 2013 Sep 13;439(1):47-53
references.pmid: 23962428
references.citation: Cytogenet Cell Genet. 2001;94(3-4):121-6
references.pmid: 11856867
references.citation: Lancet. 2003 Dec 6;362(9399):1907-17
references.pmid: 14667750
references.citation: Oncogene. 1991 Apr;6(4):659-63
references.pmid: 1851551
references.citation: Cell Growth Differ. 1995 Aug;6(8):1019-25
references.pmid: 8547216
references.citation: Carcinogenesis. 1996 May;17(5):931-8
references.pmid: 8640940
references.citation: J Biol Chem. 1997 Mar 7;272(10):6621-8
references.pmid: 9045692
references.citation: Hepatology. 1999 Jan;29(1):62-7
references.pmid: 9862851
references.citation: Endocr Relat Cancer. 2004 Dec;11(4):709-24
references.pmid: 15613447
references.citation: J Clin Invest. 2005 Feb;115(2):209-18
references.pmid: 15690074
references.citation: Cytokine Growth Factor Rev. 2005 Apr;16(2):179-86
references.pmid: 15863033
references.citation: World J Gastroenterol. 2005 Sep 14;11(34):5266-72
references.pmid: 16149130
references.citation: J Gastroenterol Hepatol. 2005 Nov;20(11):1781-7
references.pmid: 16246200
references.citation: Cancer Res. 2006 Feb 1;66(3):1481-90
references.pmid: 16452204
references.citation: J Cell Mol Med. 2006 Jan-Mar;10(1):76-99
references.pmid: 16563223
references.citation: Int J Oncol. 2006 Jul;29(1):163-8
references.pmid: 16773196
references.citation: Transplantation. 2007 Nov 27;84(10):1262-71
references.pmid: 18049111
references.citation: Oncogene. 2008 Jan 3;27(1):85-97
references.pmid: 17599042
references.citation: Int J Oncol. 2008 Aug;33(2):233-7
references.pmid: 18636142
references.citation: N Engl J Med. 2008 Jul 24;359(4):378-90
references.pmid: 18650514
references.citation: Hepatology. 2008 Oct;48(4):1312-27
references.pmid: 18821591
references.citation: J Hepatol. 2009 Jan;50(1):118-27
references.pmid: 19008009
references.citation: Nat Rev Cancer. 2010 Feb;10(2):116-29
references.pmid: 20094046