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表皮生长因子受体和转化生长因子-α对丙型肝炎病毒诱导的肝癌发生的影响。

Impact of epidermal growth factor receptor and transforming growth factor-α on hepatitis C virus-induced hepatocarcinogenesis.

作者信息

Badawy Afkar Abdel-Ghany, El-Hindawi Ali, Hammam Olfat, Moussa Mona, Gabal Samia, Said Noha

机构信息

Department of Pathology, Theodor Bilharz Research Institute, Imbaba, Egypt.

Faculty of Medicine, Cairo University, Giza, Egypt.

出版信息

APMIS. 2015 Oct;123(10):823-31. doi: 10.1111/apm.12431. Epub 2015 Aug 17.

Abstract

Epidermal growth factor receptor system plays a central hepato-protective and pro-regenerative role in liver. Transforming growth factor-α (TGF-α) is an important autocrine growth regulator of hepatocytes that plays a role in development of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC). This study was done on 40 core liver biopsies from patients with CHC, 20 liver specimens from HCC cases on top of CHC as well as five normal controls. All were immunohistochemically stained with epidermal growth factor receptor (EGFR) and TGF-α antibodies. Some selected HCC cases were submitted for FISH technique to detect EGFR gene alteration. By immunohistochemistry EGFR and TGF-α were overexpressed in HCC and cirrhotic cases compared to CHC cases without cirrhosis. Also, their expression was stronger in CHC cases with higher grades of activity and stages of fibrosis compared to lower ones. FISH positive results for EGFR were detected in 33.3% of the examined HCC cases. EGFR and TGF-α can be used as predictive markers for activity, fibrosis, and carcinogenesis in CHC patients. Overexpression of EGFR in HCC patients can be promising in selecting those who can get benefit from anti-EGFR target therapy.

摘要

表皮生长因子受体系统在肝脏中发挥着核心的肝保护和促再生作用。转化生长因子-α(TGF-α)是肝细胞重要的自分泌生长调节因子,在慢性丙型肝炎(CHC)患者的肝细胞癌(HCC)发生中起作用。本研究对40例CHC患者的肝脏穿刺活检组织、20例CHC基础上的HCC病例的肝脏标本以及5例正常对照进行了研究。所有标本均用表皮生长因子受体(EGFR)和TGF-α抗体进行免疫组织化学染色。部分选定的HCC病例进行荧光原位杂交(FISH)技术检测EGFR基因改变。免疫组织化学结果显示,与无肝硬化的CHC病例相比,HCC和肝硬化病例中EGFR和TGF-α表达上调。此外,与活动度和纤维化程度较低的CHC病例相比,活动度和纤维化程度较高的CHC病例中它们的表达更强。在33.3%的受检HCC病例中检测到EGFR的FISH阳性结果。EGFR和TGF-α可作为CHC患者活动度、纤维化和致癌作用的预测标志物。HCC患者中EGFR的过表达对于选择能从抗EGFR靶向治疗中获益的患者可能具有重要意义。

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