Protein overexpression and gene atplificntion of c-ertB-2(HER-2/neu) in human cancers

C-erb B-2异常引起了人们的极大关注，因为使用针对c-erb B-2基因产物的抗体的新疗法对c-erb B-2扩增和/或过度表达的癌症有效。因此，迫切需要了解c-erbB-2在人类各种类型癌症中的表达情况。用抗人c-erb B-2蛋白内部结构域的多克隆抗体(Nichirei)进行免疫组织化学检测，并用c-erb B-2和17号染色体着丝粒区域特异的探针进行双色荧光原位杂交(FISH)检测基因扩增。结果如下：1.乳腺癌：235例乳腺癌中52例(22.1%)可辨别。49个肿瘤有基因扩增。基因扩增与蛋白过度表达的符合率为95.7%。胃癌：在352例胃癌中，29例(8.2%)c-ETI-2蛋白过度表达。3+染色的所有家教和2+染色的5名家教中的1名均显示c-ertB-2.3的高水平扩增。肺癌：在195例肺癌(182例原发，13例转移)中，1例腺癌、1例大细胞癌和1例转移性癌有明显的细胞膜染色。两例原发癌和转移癌c-erbB-2.4基因扩增8倍以上。子宫癌：105例肿瘤中有4例同时存在过度表达和扩增。结肠癌：62例结肠癌中有3例检测到该蛋白过表达。胰腺癌：35例肿瘤中未发现c-erbB-2过表达病例。

c-erbB-2 abnormalities attract a great deal of attention because the new therapy using an antibody against the c-erbB-2 gene product is effective against cancers with amplification and/or overexpression of c-erbB-2. Therefore, there is urgent need to know c-erbB-2 status in various types of human cancers. The protein overexpression was examined iimiunohistochemically using polycloral antibody (Nichirei) against internal domain of human c-erbB-2 protein, and the gene amplification was detected by dual-color fluorescence in situ hybridization (FISH) using probes specific for c-erbB-2 and the centromeric region of chromosome 17 (Vysis). The results was follow.1.Breast cancers : Discernible imnunostaing was found in 52 (22.1 %) of 235 carcinomas analyzed. Gene amplification was found in 49 tumors. The concordance between gene amplification and protein overexpressioin was 95.7 %.2. Gastric cancers : Overexpression of c-eti」-2 protein was fctnd in 29 (8.2 %) of the 352 gastric carcinomas analyzed. All tutors with 3+ iimuiostaining and one of five tutors with 2+ staining showed high level atplification of c-ertB-2.3. Lung cancers : Distinct membrane staining was found in an adenocarcinoma, a large cell carcinoma and a metastatic carcinoma from the breast in a total of 195 pulmonary carcinomas (182 primary and 13 metastatic) examined. The two primaries and the metastatic carcinoma had more than 8-folds amplification of c-erbB-2.4. Uterine cancers : Both the overexpression and the amplification were found in four of 105 tumors examined.5. Colon cancers : The protein overexpression was detected in three of 62 cancers.6. Pancreatic cancers : No case with c-erbB-2 overexpression was found in 35 tumors examined.