title: Elevated CA19-9 Is Associated With Increased Mortality In A Prospective Cohort Of Hepatocellular Carcinoma Patients.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. CA19-9 is a glycoprotein that predicts poor prognosis in pancreatic and biliary malignancies. We evaluated it as a prognostic biomarker for patients with HCC.
  
  
  METHODS
  We prospectively enrolled 145 patients with HCC, diagnosed using American Association for Study of Liver Diseases criteria, between October 2008 and November 2012. We examined whether baseline serum CA19-9 levels predicted overall survival. We also examined immunostains of hepatic resections and explants of patients with elevated and normal serum CA19-9.
  
  
  RESULTS
  In a cohort of predominantly hepatitis C and B patients, CA19-9 ≥100 U/ml was associated with a 2.7-fold increased mortality (hazard ratio (HR): 2.72; 95% confidence interval (CI): 1.52-4.88, P<0.001). It remained a significant predictor (HR: 2.58; 95% CI: 1.41-4.72, P=0.002) in a multivariable model adjusted for Child-Pugh score, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and Model for End-Stage Liver Disease. CA19-9 immunohistochemistry performed on a subset of liver resection and explant specimens showed increased CA19-9 immunostaining of non-tumor liver parenchyma in patients with elevated serum CA19-9. It also showed staining of native and reactive bile ducts, and of progenitor-like cells at the periphery of cirrhotic nodules.
  
  
  CONCLUSIONS
  Elevated serum CA19-9 ≥100 U/ml is an independent predictor of poor overall survival in this hypothesis-generating study. The unfavorable prognosis seen with elevated serum levels may be related to progenitor-like cells in the non-tumor liver.
authors: Departments of Medicine, Columbia University, New York, New York, USA.
authors: Christine C
authors: CC
authors: Hsu
authors: Department of Epidemiology, Columbia University, New York, New York, USA.
authors: Abhishek
authors: A
authors: Goyal
authors: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
authors: Alina
authors: A
authors: Iuga
authors: Department of Radiology, Columbia University, New York, New York, USA.
authors: Saravanan
authors: S
authors: Krishnamoorthy
authors: Departments of Medicine, Columbia University, New York, New York, USA.
authors: Valerie
authors: V
authors: Lee
authors: 1] Departments of Medicine, Columbia University, New York, New York, USA [2] Department of Surgery, Columbia University, New York, New York, USA.
authors: Elizabeth C
authors: EC
authors: Verna
authors: Department of Biostatistics, Columbia University, New York, New York, USA.
authors: Shuang
authors: S
authors: Wang
authors: School of Medicine, China Medical University and Hospital, Taichung, Taiwan.
authors: Fei-Na
authors: FN
authors: Chen
authors: Departments of Medicine, Columbia University, New York, New York, USA.
authors: Rosa
authors: R
authors: Rodriguez
authors: Department of Surgery, Columbia University, New York, New York, USA.
authors: Jean
authors: J
authors: Emond
authors: Departments of Medicine, Columbia University, New York, New York, USA.
authors: Paul
authors: P
authors: Berk
authors: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
authors: Jay
authors: J
authors: Lefkowitch
authors: 1] Departments of Medicine, Columbia University, New York, New York, USA [2] Department of Surgery, Columbia University, New York, New York, USA.
authors: Lorna
authors: L
authors: Dove
authors: 1] Departments of Medicine, Columbia University, New York, New York, USA [2] Department of Surgery, Columbia University, New York, New York, USA.
authors: Robert S
authors: RS
authors: Brown
authors: 1] Departments of Medicine, Columbia University, New York, New York, USA [2] Department of Surgery, Columbia University, New York, New York, USA.
authors: Abby B
authors: AB
authors: Siegel
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