High α-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma:: Significance of hepatitis virus infection, age, p53 and β-catenin mutations
High α-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma:: Significance of hepatitis virus infection, age, p53 and β-catenin mutations
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DOI：
10.1002/ijc.20279
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发表时间：
2004-10-20
影响因子：
6.4
通讯作者：
Hsu, HC
中科院分区：
文献类型：
--
作者：
Peng, SY;Chen, WJ;Hsu, HC
甲胎蛋白（AFP）在肝细胞癌（HCC）中经常升高。本研究旨在探讨781例接受根治性肝切除术的原发性肝癌患者AFP升高的意义及相关因素。我们发现高AFP（> 200 ng/ml）与HCC中AFP mRNA表达相关（p = 0.00001），与主要临床病理因素相关。低龄化（55岁）p = 0.00001），血清中的B型肝炎表面抗原（HBsAg）（p = 0.00001），p53突变（p = 0.008），大肿瘤（p = 0.00001），血管浸润（p = 0.00001）和早期肿瘤复发（p = 0.00001）与高AFP显著相关，而血清中抗HCV和HCC中β-catenin突变的高AFP发生率较低（分别为p = 0.013和< 0.0001）。我们还发现，AFP高的HCC患者10年生存率较低（p < 0.0001），特别是大HCC患者（p < 0.0001）。在单因素分析中，高AFP（p < 0.0001）、HBsAg阳性（p = 0.05）、p53突变（p = 0.0004）、肝硬化（p = 0.0094）、大肿瘤（p = 0.0003）、血管侵犯（p < 0.0001）和早期复发（p < 0.0001）是显著的不利预后因素。在考克斯比例风险回归分析中，校正肿瘤大小和肿瘤分期的影响后，高AFP仍具有边缘显著性（OR = 1.2; CI = 1.0-1.4）（p = 0.0821）。此外，在AFP mRNA阳性HCC的肝脏中检测到AFP mRNA与更频繁的早期复发相关（p = 0.0026），并且可能是肝内扩散的有用标志物。因此，我们得出结论，AFP升高，而不是一个巧合的附带现象，似乎有助于血管浸润和肝癌的进展，并有助于确定肝癌患者的子集，肝切除术后早期复发和预后不良的风险增加。(C)2004 Wiley-Liss，Inc.
alpha-Fetoprotein (AFP) is often elevated in hepatocellular carcinoma (HCC). This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy. We showed that high AFP (> 200 ng/ml), which was associated with AFP mRNA expression in HCC (p = 0.00001), correlated with major clinicopathologic factors. Younger age (5 55 years; p = 0.00001), hepatitis B surface antigen (HBsAg) in serum (p = 0.00001), p53 mutation (p = 0.008), large tumor (p = 0.00001), vascular invasion (p = 0.00001) and early tumor recurrence (p = 0.00001) were significant associates of high AFP, while anti-HCV in serum and beta-catenin mutation in HCC had less frequent high AFP (p = 0.013 and < 0.0001, respectively). We also showed that HCC with high AFP had a lower 10-year survival (p < 0.0001), particularly in large HCC (p < 0.0001). At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p = 0.05), p53 mutation (p = 0.0004), liver cirrhosis (p = 0.0094), large tumor (p = 0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors. In Cox proportional hazards regression analysis, high AFP remained a borderline significance (OR = 1.2; CI = 1.0-1.4) after adjustment for the effect of tumor size and tumor stage (p = 0.0821). Furthermore, the detection of AFP mRNA in the liver of AFP mRNA-positive HCC was associated with more frequent early recurrence (p = 0.0026) and might be a useful marker of intrahepatic spread. We therefore conclude that AFP elevation, more than a coincidental epiphenomenon, appears to contribute to vascular invasion and HCC progression and help to identify subsets of HCC patients with increased risk for early recurrence and poor prognosis after hepatectomy. (C) 2004 Wiley-Liss, Inc.