Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection

J Hepatol. 2011 Mar;54(3):497-505. doi: 10.1016/j.jhep.2010.07.044. Epub 2010 Oct 1.


Background & aims: Neutrophil infiltration has been linked to clinical outcome of various cancer types. However, its role in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated prognostic values for intratumoral and peritumoral neutrophils in HCC patients undergoing curative resection.

Methods: The expression of CD66b, CD8, TGF-beta, and CD34 was assessed by immunohistochemistry in tissue microarrays containing paired intratumoral and peritumoral tissues from 197 patients receiving curative resection for HCC. Prognostic values for these and other clinicopathologic factors were evaluated.

Results: Intratumoral CD66b(+) neutrophils significantly correlated with CD8(+) T cells (r=0.240, p=0.004), TGF-beta expression (p=0.012), BCLC stage (p=0.016), and early recurrence (p=0.041). Increased intratumoral neutrophils were significantly associated with decreased RFS/OS (p=0.001 and p<0.001, respectively) in univariate analysis and were identified as an independent prognostic factor (HR=1.845, 95% CI=1.169-2.911, p=0.008 for RFS; HR=2.578, 95% CI=1.618-4.106, p<0.001 for OS) in multivariate analysis. Intratumoral neutrophil-to-CD8(+) T cell ratio (iNTR) better predicted the outcome in terms of minimum p values. Intratumoral neutrophils were also demonstrated to be statistically predictive for RFS/OS in the normal AFP subgroup, small HCC subgroup, and validation cohort. However, peritumoral neutrophils were not associated with the outcome of HCC.

Conclusions: The presence of intratumoral neutrophils was a poor prognostic factor for HCC after resection. Intratumoral neutrophil-to-CD8(+) T cell ratio was a better predictor of outcome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • CD8 Antigens / metabolism
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Cell Adhesion Molecules / metabolism
  • Cohort Studies
  • Female
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness / immunology
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Neutrophil Infiltration*
  • Neutrophils / immunology
  • Neutrophils / pathology*
  • Prognosis
  • Transforming Growth Factor beta / metabolism


  • Antigens, CD
  • Antigens, CD34
  • CD8 Antigens
  • CEACAM8 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • Transforming Growth Factor beta