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原发性肝癌中ErbB1和ErbB2表达用于治疗靶点的研究。

Investigation of ErbB1 and ErbB2 expression for therapeutic targeting in primary liver tumours.

作者信息

Altimari A, Fiorentino M, Gabusi E, Gruppioni E, Corti B, D'Errico A, Grigioni W F

机构信息

Pathology Unit of the F.Addarii Institute of Oncology, Department of Oncology and Hematology, University of Bologna, Viale Ercolani 412, 40138 Bologna, Italy.

出版信息

Dig Liver Dis. 2003 May;35(5):332-8. doi: 10.1016/s1590-8658(03)00077-x.

DOI:10.1016/s1590-8658(03)00077-x
PMID:12846405
Abstract

BACKGROUND

Molecular targets are needed for primary liver tumours.

AIMS

ErbB1 and ErbB2 expression was analysed in neoplastic and surrounding tissue in surgical specimens from 52 hepatocellular carcinomas and 48 intrahepatic cholangiocarcinomas, randomly chosen from cases surgically treated in this institution.

METHODS

ErbB1 and ErbB2 expression were evaluated immunohistochemically, the latter by Herceptest. Gene amplification of ErbB2 was tested by chromogenic in situ hybridisation.

RESULTS

In normal/cirrhotic non-neoplastic tissue, the ErbB1 (but not ErbB2) antibody commonly stained normal hepatocytes and mature intrahepatic ducts. In neoplastic tissue, moderate/strong ErbB1 immunostaining occurred in 43/52 (85%) hepatocellular carcinomas and 39/48 (81%) intra-hepatic cholangiocarcinomas. With ErbB2 Herceptest, 0/52 (0%) hepatocellular carcinomas and 2/48 (4%) intra-hepatic cholangiocarcinomas had treatable scores of 2+/3+ (chromogenic in situ hybridisation confirmed gene amplification in the latter two cases only). Neither ErbB1 nor ErbB2 expression correlated with any of the main clinical-pathologic features or survival.

CONCLUSIONS

Although not related to prognosis, ErbB1 could be a molecular target in a large percentage of patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma. Inclusion of anti-ErbB1 drugs such as ZD 1839 and c225 (and possibly also anti-ErbB2 drugs like Trastuzumab for a small subset of patients) in clinical trials is suggested.

摘要

背景

原发性肝癌需要分子靶点。

目的

分析52例肝细胞癌和48例肝内胆管癌手术标本中肿瘤组织及周围组织的ErbB1和ErbB2表达情况,这些标本是从本机构手术治疗的病例中随机选取的。

方法

采用免疫组织化学方法评估ErbB1和ErbB2表达,后者采用赫赛汀检测法。通过显色原位杂交检测ErbB2的基因扩增情况。

结果

在正常/肝硬化非肿瘤组织中,ErbB1抗体(而非ErbB2抗体)通常可使正常肝细胞和成熟肝内胆管染色。在肿瘤组织中,43/52例(85%)肝细胞癌和39/48例(81%)肝内胆管癌出现中度/强ErbB1免疫染色。采用ErbB2赫赛汀检测法,0/52例(0%)肝细胞癌和2/48例(4%)肝内胆管癌的治疗评分为2+/3+(显色原位杂交仅证实后两例存在基因扩增)。ErbB1和ErbB2表达均与任何主要临床病理特征或生存率无关。

结论

尽管与预后无关,但ErbB1可能是大部分肝细胞癌或肝内胆管癌患者的分子靶点。建议在临床试验中纳入抗ErbB1药物如ZD 1839和c225(对于一小部分患者可能还包括抗ErbB2药物如曲妥珠单抗)。

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