Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor

Cancer. 2008 Jun 15;112(12):2740-8. doi: 10.1002/cncr.23488.


Background: Few studies have investigated the pathologic types and prognosis of hepatocellular carcinoma (HCC) with lymph node metastasis (LNM). The purpose was to explore pathologic types and pertinent therapy of HCC with LNM.

Methods: An immunohistochemical study for CK19 and OV-6 was performed on tissue microarrays of HCC with LNM (n=47) and those without LNM (n=125). The clinicopathologic factors and patient survival were analyzed.

Results: Immunopositivity of CK19 and OV-6 in HCC with LNM were higher than that in 125 HCC without LNM (27.7% vs 5.6%, P=.000; 29.8% vs 12.8%, P=.009); their expressions were significantly correlated in HCC with LNM (correlation coefficient: 0.637, P=.000). The CK19 expression and tumor (T) classification of American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) tumor staging system were 2 independent risk factors for developing LNM (odds ratio [OR], 5.170, 95% confidence interval [CI], 1.840-14.528, P=.002; OR, 1.879, 95% CI, 1.236-2.857, P=.003). The CK19(+) group had shorter median survival (7.7 months vs 21.7 months, P=.013); CK19 expression was the independent prognostic factor for overall survival in HCC with LNM and was correlated with proliferating cell nuclear antigen labeling index and matrix metalloproteinase-9 expression (correlation coefficient: 0.484, P=.001 and 0.459, P=.001, respectively).

Conclusions: CK19 expression and AJCC/UICC T classification were 2 independent risk factors for developing LNM in HCC. CK19 expression was the independent prognostic factor for HCC with LNM. It is of clinical significance for treatment modalities to differentiate HCC with intrahepatic cholangiocarcinoma-like differentiation (CK19[+]) from one with a higher T classification (CK19[-]).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Differentiation / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Female
  • Hepatectomy
  • Humans
  • Keratin-19 / metabolism*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Lymphatic Metastasis / pathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Prognosis
  • Proliferating Cell Nuclear Antigen / metabolism
  • Risk Factors


  • Antigens, Differentiation
  • Keratin-19
  • Proliferating Cell Nuclear Antigen
  • oval cell marker OV-6
  • Matrix Metalloproteinase 9