Ets-1原癌基因的表达与人类肝细胞癌的细胞分化相关。

Kanda Kazuaki, Nakayama Toshiyuki, Onizuka Shinya, Tomioka Tsutomu, Kanematsu Takashi

Department of Surgery II, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

Hepatogastroenterology. 2002 May-Jun;49(45):747-51.

BACKGROUND/AIMS: Ets-1 regulates the expression of a number of genes related to remodeling of the extracellular matrix. Ets-1 is associated with the occurrence of invasive processes, proliferation and differentiation. Less is known about the biological functions of Ets-1 in human hepatocellular carcinoma. In an attempt at elucidation, we examined immunohistochemically hepatocellular carcinoma followed by application of genetic techniques.

METHODOLOGY

We performed immunohistochemical analysis on tissue from 59 Japanese patients undergoing surgical resection of hepatocellular carcinoma using the antibody against human Ets-1. We compared Ets-1 expression in relation to clinicopathological findings. In situ hybridization and reverse transcription-polymerase chain reaction were also performed to confirm the expression of Ets-1 messenger RNA in hepatocellular carcinoma tissues.

RESULTS

In specimens from 59 patients with hepatocellular carcinoma, 41 (70%) showed positive staining for Ets-1 protein. The expression of Ets-1 messenger RNA was also observed in hepatocellular carcinoma tissues by in situ hybridization and reverse transcription-polymerase chain reaction. The expression of Ets-1 correlated with histological differentiation of hepatocellular carcinoma (P < 0.05). Ets-1 was positive in 2 (50%) of the 4 well-differentiated hepatocellular carcinomas and in 28 (64%) of the 44 moderately differentiated hepatocellular carcinomas, whereas all the 11 poorly differentiated hepatocellular carcinomas were positive for Ets-1 staining. Ets-1 protein was expressed more strongly at the peripheral than the central area of the tumor. Otherwise, no particular correlation was evident in terms of clinicopathological factors.

CONCLUSIONS

We found Ets-1 to be expressed in human hepatocellular carcinoma, particularly at the peripheral area of the tumor. As this expression is linked to cell differentiation, this gene may yield biological information relative to this malignant tumor of the liver.

背景/目的：Ets-1调节许多与细胞外基质重塑相关的基因的表达。Ets-1与侵袭过程、增殖和分化的发生有关。关于Ets-1在人类肝细胞癌中的生物学功能知之甚少。为了阐明这一点，我们对肝细胞癌进行了免疫组织化学检查，随后应用了基因技术。

方法

我们使用抗人Ets-1抗体对59例接受肝细胞癌手术切除的日本患者的组织进行了免疫组织化学分析。我们比较了Ets-1表达与临床病理结果的关系。还进行了原位杂交和逆转录-聚合酶链反应以确认Ets-1信使核糖核酸在肝细胞癌组织中的表达。

结果

在59例肝细胞癌患者的标本中，41例（70%）Ets-1蛋白染色呈阳性。通过原位杂交和逆转录-聚合酶链反应也在肝细胞癌组织中观察到了Ets-1信使核糖核酸的表达。Ets-1的表达与肝细胞癌的组织学分化相关（P<0.05）。在4例高分化肝细胞癌中有2例（50%）Ets-1呈阳性，在44例中分化肝细胞癌中有28例（64%）Ets-1呈阳性，而11例低分化肝细胞癌的Ets-1染色均为阳性。Ets-1蛋白在肿瘤周边区域的表达比中央区域更强。此外，在临床病理因素方面没有明显的特定相关性。