[Nuclear accumulation of CXCR4 and overexpressions of VEGF-C and CK19 are associated with a higher risk of lymph node metastasis in hepatocellular carcinoma].
OBJECTIVE
The aim of this study was to evaluate the correlation of protein expressions of CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor-C (VEGF-C) and cytokeratin 19 (CK-19) with lymph node metastasis (LNM) in patients with hepatocellular carcinoma (HCC), and their survival.


METHODS
The expressions of CXCR4, VEGF-C and CK-19 in HCC patients with (n = 123) or without (n = 145) LNM were determined using tissue microarray and immunohistochemical staining. The relationship between clinicopathological features and CXCR4, VEGF-C and CK-19 were analyzed. Evaluation of immunostaining was performed semiquantitatively by visual assessment.


RESULTS
The UICC T stage, and expressions of nuclear CXCR4, VEGF-C and CK-19 were independent risk factors for LNM. Nuclear CXCR4, VEGF-C and CK-19 expression were predictive factors for LNM in HCC patients. In patients with LNM, the median survival time was 15.1 months for patients with high nuclear CXCR4 expression and 24.5 months for those with low nuclear CXCR4 expression. The median survival time was 15.1 months for patients with high tumor VEGF-C expression and 31.1 months for those with low tumor VEGF-C expression. The median survival time was 12.0 months for patients with positive CK-19 expression and 19.2 months for patients with negative CK-19 expression. Patients with high nuclear CXCR4, VEGF-C or CK-19 expression had significantly poorer prognosis than those with low expression (all P < 0.05). PVT, UICC T stage and expressions of nuclear CXCR4, VEGF-C, and CK-19 were independent prognostic factors.


CONCLUSIONS
Increased protein expressions of nuclear CXCR4, VEGF-C, and CK-19 are independent risk factors for developing lymph node metastasis, and they are significantly correlated with LNM and poor outcome in HCC patients.
Xiang
Zuo-lin
ZL
Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zeng
Zhao-chong
ZC
Tang
Zhao-you
ZY
Fan
Jia
J
Sun
Hui-chuan
HC
Wu
Wei-zhong
WZ
Tan
Yun-shan
YS
D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012307:Risk Factors; D015996:Survival Rate; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
C527276:CXCR4 protein, human; D053539:Keratin-19; D019718:Receptors, CXCR4; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C