Yuen M F, Wu P C, Lai V C, Lau J Y, Lai C L
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China.
Cancer. 2001 Jan 1;91(1):106-12. doi: 10.1002/1097-0142(20010101)91:1<106::aid-cncr14>3.0.co;2-2.
Increased expression of the proto-oncogene c-myc is a common phenomenon in hepatocellular carcinoma (HCC). The proto-oncogenes c-fos and c-jun are involved in cell cycle progression and cellular proliferation.
The objective of this study was to elucidate the mechanism of hepatocarcinogenesis with regard to the expressions of c-myc, c-fos, and c-jun. One hundred fifty biopsied HCC specimens were stained immunohistochemically for the above phenotypic markers both in tumor tissue and in adjacent nontumor tissue.
Although the expression of c-myc was high (74%) in tumor tissue, it was significantly less compared with the expression in nontumor tissue (100%; P = 0.0002). The expression of c-myc was inversely proportional to the grade of differentiation in tumor tissue (P = 0.0108; correlation coefficient [r] = -0.244); that is, tissue with poorer histologic differentiation had a lower level of c-myc expression. There were inverse associations between the expression of c-myc and the expression of mutated p53 (P = 0.0017; r = -0.285) as well as the expression of Ki67 (P = 0.057; r = -0.147). There was significantly high expression of c-fos in tumor tissue compared with the expression in nontumor tissue (91% vs. 0%; P < 0.0001). Both the tumor tissue and the nontumor tissue had high levels of expression of c-jun (96.53% and 100%, respectively). There was a trend toward a positive association between the expression of c-fos and the expression of c-jun in tumor tissue (P = 0.07; r = 0.162).
Because c-myc is a known inducer of wild type p53, decreased c-myc expression may lead to uncontrolled cell growth because of the lack of p53 expression that normally induces apoptosis. The coordinated expression of c-fos and c-jun in HCC may reflect the coordinated tumor cell cycle of progression and proliferation; however, future studies are required to elucidate this possibility.
原癌基因c-myc的表达增加是肝细胞癌（HCC）中的常见现象。原癌基因c-fos和c-jun参与细胞周期进程和细胞增殖。
本研究的目的是阐明c-myc、c-fos和c-jun的表达在肝癌发生机制中的作用。对150例肝癌活检标本的肿瘤组织和相邻非肿瘤组织进行上述表型标志物的免疫组织化学染色。
虽然c-myc在肿瘤组织中的表达较高（74%），但与非肿瘤组织中的表达相比明显较低（100%；P = 0.0002）。c-myc的表达与肿瘤组织的分化程度呈负相关（P = 0.0108；相关系数[r] = -0.244）；也就是说，组织学分化较差的组织c-myc表达水平较低。c-myc的表达与突变型p53的表达（P = 0.0017；r = -0.285）以及Ki67的表达（P = 0.057；r = -0.147）之间呈负相关。与非肿瘤组织中的表达相比，肿瘤组织中c-fos的表达显著较高（91%对0%；P < 0.0001）。肿瘤组织和非肿瘤组织中c-jun的表达水平均较高（分别为96.53%和
100%）。肿瘤组织中c-fos的表达与c-jun的表达之间有正相关趋势（P = 0.07；r = 0.162）。
由于c-myc是野生型p53的已知诱导剂，c-myc表达降低可能导致细胞生长失控，因为缺乏正常诱导细胞凋亡的p53表达。肝癌中c-fos和c-jun的协同表达可能反映了肿瘤细胞周期进程和增殖的协同作用；然而，需要进一步的研究来阐明这种可能性。
