摘要
目的探讨结节边缘小胆管反应（DR）缺失在鉴别具有乙型肝炎肝硬化背景的小肝癌中的作用。方法对20份早期肝癌（直径≤3cm）、26份进展期肝癌（直径〉3cm）、20份高级别不典型增生结节（HGDNs）、26份低级别不典型增生结节（LGDNs）及20份因肝硬化脾大行肝活组织检查的肝硬化组织（约1cm×1cm）分别进行细胞角蛋白（CK）7和CK19免疫组织化学染色。观察两种蛋白在不同肝细胞性结节中的表达情况，并进行半定量分析。收集患者相关的临床资料。计数资料组间比较用配对χ2检验及Fisher’s接概率法检验；抗体与临床资料间的相关性用Pearson相关分析；评判DR的诊断价值用z检验；Kaplan-Meier生存曲线的比较用Logrank检验；计量资料的比较用独立样本t检验。结果对112例患者随访41．59（3～90）个月。CK7及CK19在DR的肝胆管细胞胞质中阳性，此外在小叶间胆管及少部分肝细胞中也阳性。DR分布于肝细胞性结节周围，DR缺失或减少可以显示不明显的微浸润。DR／CK7和DR／CK19在LGDNs和肝硬化组织中DR均表现为强阳性，DR在大部分HGDNs中阳性表达，而在大部分早期肝癌及进展期肝癌中缺失。统计学分析显示：DR／CK19在早期肝癌中的缺失率高于HGDNs、LGDNs及肝硬化组（校正χ2值分别为9．10，16．83，12．10，P值均〈0．01）；DR／CK7的缺失率在早期肝癌中低于进展期肝癌（校正χ2=5．17，P〈0．05），明显高于LGDNs及肝硬化组（校正χ2值分别为8．05，10．24，P值均〈0．01）。DR／CK7与DR／CK19的受试者工作特征曲线下面积很接近（Z=0．09，P〉0．05）。Pearson相关分析结果显示，DR／CK7、DR／CK19与无瘤生存时间呈正相关（r=0．541，0．552，P值均〈0．01），与早期复发时间（，值分别为-0．387，-0．413，P值均〈0．01）及病死率（r值分别为-0．446，-0．507，P值均〈0．01）呈负相关。生存分析显示，DR的缺失可提示完全生存率和无瘤生存率明显降低（P〈0．01），发生早期复发的概率明显升高（P〈0．01）。结论DR／CK7、DR／CK19的缺失均可以显示早期肝癌的微浸润，因此可以用于鉴别早期肝癌与HGDNs；DR的缺失还提示预后不良。
Objective To investigate the role of absent ductular reaction （DR） at hepatocellular- stromal boundaries in early stage hepatocellular carcinoma （HCC） with cirrhosis in patients with chronic hepatitis B. Methods Cytokeratin （CK）7 and CK19 expression was detected by the SP immunohistochemistry method in 112 hepatic nodules taken from 20 cases of early HCC, 26 cases of HCC with nodules 〉 3 cm, 20 cases of high-grade dysplastic nodule （HGDN）, 26 cases of low-grade dysplastic nodule （LGDN）, and 20 cases of cirrhosis （CIR）. DR/CK7 and DR/CK19 were assessedseparately on a semi-quantitative scale and statistically analyzed. Results The mean age of the patients in the study was 53.71 years-old, and the study population consisted of 73 males and 39 females. The follow- up time ranged fxom 3 to 90 months. Positive CK7 and CK19 staining was detected in the cytoplasm of DR- positive hepatobiliary cells, interlobular bile duct, and a portion of hepatic cells. All of the DR/CK7- and DR/CK19-positive cells were localized around the non-invasive nodules. Specimens with focal or diffuse DR/CK7- and DR/CK19-1oss had more robust stromal invasion. Specimens from early HCC cases showed greater DR/CK19 loss than specimens from HGDN cases, LGDN cases and CIR cases （all P 〈 0.01）. DR/ CK7 loss of early HCC was less than HCC with nodules 〉 3 cm （P 〈 0.05）, and more than LGDN cases and CIR cases （both P 〈 0.01）.The area under the receiver operating characteristic curve of DR/CK7 was very similar to that ofDR/CK19 （P 〉 0.05）. Pearson＇s correlation analysis indicated that DR/CK7 and DR/CK19 were positively correlated with tumor-free time （P 〈 0.01） and negatively correlated with early recurrence time as well as death rate （bothP 〈 0.01）. Furthermore, cases showing DR/CK7 or DR/CK19 loss had lower overall survival rate and tumor-free survival rate （P 〈 0.01） and higher early recurrence rate （P 〈 0.01）. Conclusion DR/CK7 and DR/CK19 immunostaining may help to distinguish non-invasive HGDNs from both minimally-invasive and overtly-invasive HCCs by identifying small foci of invasion and predicting increased risk of invasiveness.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2013年第12期924-928,共5页
Chinese Journal of Hepatology
基金
天津市重点科技攻关专项基金（05YFSZSF02500）.
关键词
癌
肝细胞
诊断
鉴别
小胆管反应
间质浸润
Carcinoma, hepatocellular
Diagnosis, differential
Ductular reaction
Stromal invasion
