甲状腺转录因子-1在肝细胞性肝癌中的表达

Expression of thyroid transcription factor-1 in hepatocellular carcinoma

目的探讨甲状腺转录因子-1(TTF-1)在肝细胞性肝癌(HCC)的诊断及其生物学行为判定中的价值。方法良性病变切除的肝脏标本30例,其中肝硬化及炎症性病变25例,腺瘤5例。肝脏肿瘤标本176例,其中HCC142例(高分化12例、中分化57例、低分化73例,肝内胆管细胞癌(ICC)17例,肝脏转移癌(MC)17例。应用免疫组化法分别检测TTF-1在上述不同组织中的表达;运用Fishers精确检验、Kruskal-Wallis检验及Spearman等级相关分析,比较不同组织中TTF-1表达的差异。结果在所有良性病变和癌旁组织的肝细胞胞质中,TTF-1均呈强阳性表达。肝脏肿瘤标本中,HCC组织中TTF-1表达阳性率为78.9%(112/142),而ICC和MC组织中TTF-1表达均为阴性(均P<0.0001)。TTF-1在高分化、中分化和低分化HCC中的阳性表达率分别为100%、98.2%和60.2%;Spearman等级相关分析表明,TTF-1表达与肿瘤分化程度密切相关(P=0.0001)。结论TTF-1在HCC中的表达具有较强的特异性,可作为其诊断及与其他类型肿瘤或转移性癌鉴别诊断的重要标记物。TTF-1表达的缺失可能在HCC细胞去分化过程中起重要作用。

Objective To investigate the value of thyroid transcription factor-1 （TTF-1） in the diagnosis and biological behavior assessment of hepatocellular carcinoma （HCC）. Methods Thirty liver specimens obtained from benign lesions were analysed, among which 25 were hepatic cirrhosis and inflammatory diseases, and the other 5 were adenomas. And there were 176 specimens of liver tumors, among which 142 were HCC （well differentiated, n = 12 ; moderately differentiated, n = 57 ; poorly differentiated, n = 73） , 17 were intrahepatic cholangiocellular carcinoma （ICC） and the other 17 were liver metastatic carcinoma （MC）. The expression of TTF-1 was examined immunohistochemically in the above tissues, and the difference in expression of TTF-1 among different tissues was examined by Fisher＇s exact test, Kruskal-Wallis test and Spearman rank correlation analysis. Results TTF-1 was significantly expressed in the cytoplasms of all the hepatocytes besides tumors and liver benign lesions. The expression rate of TTF-1 in HCC was 78.9% （112/142） , however, TTF-1 was negatively expressed in ICC and MC（P 〈0.0001 for both）. The expression rate of TTF-1 in well-differentlated, moderatelydifferentiated and poorly-differentiated HCC were 100% , 98.2% and 60.2% , respectively. It was revealed by Spearman rank correlation analysis that the expression of TTF-1 was significantly associated with the tumor differentiation （P = 0. 0001 ）. Conclusion TTF-1 is specifically expressed in HCC, and can serve as an important marker in the diagnosis and differential diagnosis. The deletion of TTF-1 protein may play an important role in the dedifferentiation of the tumor cells.