Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications.
Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications.
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发表时间：
1996-10
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通讯作者：
P. Wu;Jane Wing-Sang Fang;Victor Kar-Tai Lau;Ching. Lai;C. Lo;Johnson Yiu-Nam Laut
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作者：
P. Wu;Jane Wing-Sang Fang;Victor Kar-Tai Lau;Ching. Lai;C. Lo;Johnson Yiu-Nam Laut
肝细胞癌是一种异质性疾病。不同分化阶段的肝细胞癌具有不同的临床和病理生物学行为。为了验证根据其表型标志(肝细胞分化和胆管分化)将肝细胞癌分为两种类型的假设，研究了290例中国人肝细胞癌患者的肝组织。免疫组织化学方法检测肝细胞分化标记物(Hep-PAR反应抗原)、胆汁分化标记物(AE1-AE3、细胞角蛋白-19)、增殖标记物(Ki-67、增殖细胞核抗原)、甲胎蛋白、P53、转化生长因子-α在肿瘤组织中的表达。肝细胞分化标志物阳性率为99.7%，胆系分化标志物阳性率为29.3%。临床上，没有胆汁标志物阳性的肝癌患者存活超过27周，相比之下，胆汁标志物阴性的肝癌患者存活率为22.6%。胆汁分化标志物阳性的肝癌细胞分化程度较低(P<；0.001)，增殖标志物高表达(Ki-67，P<；0.001；增殖细胞核抗原，P=0.0114)，具有更强的侵袭性。胆汁标志物阳性的人肝细胞癌甲胎蛋白(P<；0.001)和p53的表达水平也较高(P=0.0077)。根据其表型(分化)标志物对肝癌进行分类具有临床和病理生物学意义。
Hepatocellular carcinoma (HCC) is a heterogeneous disease. HCC derived from different stages of cellular differentiation may have different clinical and pathobiological behavior. To test the hypothesis that HCC can be classified into two types based on its phenotypic markers (hepatocellular and biliary differentiation), liver tissues from 290 Chinese patients with HCC were studied. Expression of hepatocytic differentiation marker (HEP-PAR-reactive antigen), biliary differentiation markers (AE1-AE3, cytokeratin-19), proliferation markers (Ki-67, proliferating cell nuclear antigen), alpha-fetoprotein, p53, and transforming growth factor-alpha in the tumor tissue were assessed by immunohistochemistry. Hepatocytic differentiation marker was detected in 99.7% and biliary differentiation markers were detected in 29.3% of these tumors. Clinically, no patient with HCC with biliary markers survived for more than 27 weeks compared with a 22.6% survival rate in patients with HCC negative for biliary markers. HCCs positive for the biliary differentiation markers showed features of more aggressive disease in terms of poorer cellular differentiation (P < 0.001) and high-level expression of proliferation markers (Ki-67, P < 0.001; proliferating cell nuclear antigen, P = 0.0114) compared with HCCs without biliary markers. HCCs with biliary markers also had a higher level of expression of alpha-fetoprotein (P < 0.001) and p53 (P = 0.0077). Classification of HCCs based on its phenotypic (differentiation) markers has both clinical and pathobiological implications.