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人类胰腺癌中的c-erb B-2原癌基因。

The c-erb B-2 proto-oncogene in human pancreatic cancer.

作者信息

Hall P A, Hughes C M, Staddon S L, Richman P I, Gullick W J, Lemoine N R

机构信息

ICRF Molecular Oncology Group, Hammersmith Hospital, London, U.K.

出版信息

J Pathol. 1990 Jul;161(3):195-200. doi: 10.1002/path.1711610305.

DOI:10.1002/path.1711610305
PMID:2202801
Abstract

The c-erb B-2 oncogene encodes a 190 kD transmembrane growth factor receptor which is closely related to the EGF receptor and has been found to be amplified and overexpressed in a number of human adenocarcinomas, particularly of the breast. We have analysed, by immunocytochemistry using the 21N antibody, expression of c-erb B-2 in a retrospective series of pancreatic adenocarcinoma, chronic pancreatitis, and examples of histologically normal pancreas. In three cases (21 per cent) of chronic pancreatitis, there were focal areas of cytoplasmic immunoreactivity in regenerating epithelium. In 15 cases (17 per cent) of pancreatic adenocarcinoma, cytoplasmic immunoreactivity was seen, while in two cases (2 per cent) strong membrane staining of tumour cells was seen which could be blocked by peptide controls. c-erb B-2 immunoreactivity was also demonstrated using a second antibody, 20N, which recognizes another peptide sequence of the c-erb B-2 protein. There was no relationship between immunoreactivity and histological subtype or grade, but there was absolute concordance between staining in primary and metastatic deposits. Since the rat homologue (neu) of the c-erb B-2 oncogene may be activated by a specific point mutation in its transmembrane region, we have analysed 23 cases from this series for mutations by polymerase chain reaction amplification and sequence-specific oligonucleotide hybridization. We were unable to identify activity mutations in this series. These data suggest that there is abnormal expression of c-erb B-2 oncogene in nearly 20 per cent of cases although mutational activation of this gene is not seen in human pancreatic adenocarcinoma.

摘要

c-erb B-2癌基因编码一种190kD的跨膜生长因子受体,它与表皮生长因子(EGF)受体密切相关,并且已发现在许多人类腺癌中被扩增和过度表达,尤其是乳腺癌。我们使用21N抗体通过免疫细胞化学分析了回顾性系列胰腺腺癌、慢性胰腺炎以及组织学正常胰腺标本中c-erb B-2的表达。在3例(21%)慢性胰腺炎中,再生上皮中有局灶性细胞质免疫反应性区域。在15例(17%)胰腺腺癌中可见细胞质免疫反应性,而在2例(2%)中可见肿瘤细胞膜强染色,其可被肽对照阻断。使用识别c-erb B-2蛋白另一个肽序列的第二抗体20N也证实了c-erb B-2免疫反应性。免疫反应性与组织学亚型或分级之间无相关性,但原发灶和转移灶的染色完全一致。由于c-erb B-2癌基因的大鼠同源物(neu)可能通过其跨膜区域的特定点突变而被激活,我们通过聚合酶链反应扩增和序列特异性寡核苷酸杂交分析了该系列中的23例病例的突变情况。我们在该系列中未能鉴定出活性突变。这些数据表明,尽管在人类胰腺腺癌中未观察到该基因的突变激活,但近20%的病例中存在c-erb B-2癌基因的异常表达。

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