Use of Cytokeratin-19 Concentration to Assess Early Recurrence and Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma following Radical Resection in Patients with a Low Serum Alpha-Fetoprotein Concentration

利用细胞角蛋白-19浓度评估乙型肝炎病毒相关肝细胞癌根治术后血清甲胎蛋白浓度低的患者早期复发和预后

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Abstract

Cytokeratin 19 (CK-19) is a prognostic indicator of recurrence and metastasis of hepatocellular carcinoma (HCC) following radical resection. To investigate the role of CK-19 in assessment of early recurrence and prognosis in patients with hepatitis B virus (HBV)-related HCC following radical resection. In total, 235 patients with HBV-related HCC (age, 15-82 years; mean age, 54 ± 10 years) undergoing radical resection were screened for inclusion from January 2005 to December 2010. Malignant tissues and adjacent non-malignant tissues were sampled during surgery, and CK-19 and Ki-67 expression was determined by tissue microarray and immunohistochemistry. CK-19 mRNA levels in 30 randomly selected frozen HCC specimens were examined by reverse transcription polymerase chain reaction from January 2011 to June 2011. Correlations of CK-19 and Ki-67 expression with tumor recurrence, metastasis, disease-free survival (DFS), and overall survival (OS) were analyzed. Elevated CK-19 expression was correlated with early recurrence (P = 0.001), shorter DFS (P = 0.001), and reduced OS (P = 0.010). CK-19 expression was correlated with the Ki-67 index (P = 0.037), histological differentiation (P = 0.016), focal number (P = 0.044), and blood vessel tumor embolism (P = 0.002). Patients with metastasis within 1 year exhibited stronger CK-19 expression than did patients without metastasis (P < 0.05). Furthermore, early recurrence was associated with elevated CK-19 mRNA levels (χ2 = 5.761, P = 0.016).When confirmed by a low alpha-fetoprotein concentration (<400 μg/L), CK-19 expression in surgical biopsy specimens taken from patients with HCC during radical resection is an additional valuable indicator of early recurrence, distant metastasis, and poor prognosis in HBV-positive patients.

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