...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Modern Pathology >Determination of Her-2|[sol]|Neu Status in Breast Carcinoma: Comparative Analysis of Immunohistochemistry and Fluorescent In Situ Hybridization
【24h】

Determination of Her-2|[sol]|Neu Status in Breast Carcinoma: Comparative Analysis of Immunohistochemistry and Fluorescent In Situ Hybridization

机译：乳腺癌Her-2 | [sol] | Neu状态的测定：免疫组织化学和荧光原位杂交的比较分析

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Her-2eu (H2N) status in breast carcinoma has been considered a prognostic factor that may have therapeutic implications; however, the correlation between H2N overexpression and gene amplification has not been completely defined. A consecutive series of ductal carcinomas (34 invasive and 7 in situ) were analyzed by fluorescent in situ hybridization for H2N gene and chromosome 17 copy number using touch preps of intact cells and by immunohistochemistry, using three different commercial antibodies to H2N protein (Zymed, clone 31G7; Ventana, clone CB11; and Dako, polyclonal) in corresponding formalin-fixed, paraffin-embedded tissue sections. Gene amplification was classified as unequivocal if more than five signals were present in more than 80% of the counted nuclei and absent if more than 80% of the nuclei counted contained two or fewer gene copies. Cases that did not fulfill the above criteria were considered equivocal for amplification. Immunostaining was classified as follows: 0 = no staining; 1+ = faint, incomplete membranous pattern; 2+ = moderate, complete membranous pattern; 3+ = strong membranous pattern. Of the 34 invasive tumors, 10 (29%) had unequivocal gene amplification. Furthermore, all had more than 10 copies of the gene in more than 60% of the counted nuclei. An additional nine cases (26%) had equivocal amplification, which was usually the result of chromosome 17 aneuploidy (seven of nine) or heterogeneity. With the Zymed and Dako antibodies, all tumors with 3+ staining had unequivocal gene amplification and all cases with 2+, 1+, or 0 staining were negative or equivocal for gene amplification. With the Ventana antibody, all cases with 3+ staining had unequivocal gene amplification, but two cases with unequivocal amplification by fluorescent in situ hybridization exhibited 1+ staining. Moderate (2+) H2N staining was observed in one case, three cases, and five cases with the Ventana, Dako, and Zymed reagents, respectively, and did not correlate with H2N gene copy number. Discordance between H2N and chromosome 17 copy number was not a useful means of defining amplification. Two cases of ductal carcinoma in situ with the Zymed antibody and two with the Dako antibody showed 3+ staining despite lack of unequivocal gene amplification. We conclude that (1) strong H2N immunostaining is highly associated with gene amplification, although there is minor variation in sensitivity between different antibodies; (2) a subset of breast carcinomas (3 to 15%) demonstrate moderate H2N staining without evidence of amplification, and it is unclear whether they represent highly sensitive staining or are a subset of cases that show overexpression without amplification; (3) gene amplification, as detected by fluorescent in situ hybridization, is associated with at least 10 gene copies per nucleus, and lower gene copy duplication (3 to 4ucleus) is frequent, usually the result of chromosome 17 polysomy, and not associated with high-level overexpression; (5) overexpression of H2N without amplification may be more frequent in ductal carcinoma in situ, implying a different role in the biology of preinvasive versus invasive neoplasm.
机译：乳腺癌中Her-2 / neu（H2N）的状态被认为是可能具有治疗意义的预后因素。但是，H2N过表达与基因扩增之间的相关性尚未完全定义。使用完整细胞的触摸制备物，通过荧光原位杂交检测H2N基因和17号染色​​体的拷贝数，并通过免疫组化，使用针对H2N蛋白的三种不同商业抗体，对连续系列的导管癌（34例浸润癌和7例原位癌）进行了分析。克隆31G7; Ventana，克隆CB11; Dako，多克隆）在相应的福尔马林固定，石蜡包埋的组织切片中。如果在超过80％的计数核中存在五个以上的信号，则将基因扩增分类为明确的;如果在超过80％的核中包含两个或更少的基因拷贝，则基因扩增不存在。不符合上述条件的病例被视为模棱两可。免疫染色分类如下：0 =无染色; 1+ =微弱，不完整的膜状模式; 2+ =中等，完整的膜模式; 3+ =强膜型。在34种浸润性肿瘤中，有10种（29％）具有明确的基因扩增。此外，在超过60％的计数核中，所有基因都具有10个以上的基因拷贝。另外9例（26％）出现模棱两可的扩增，通常是17号染色​​体非整倍性（九分之七）或异质性的结果。使用Zymed和Dako抗体，所有3+染色的肿瘤均具有明确的基因扩增，所有2 +，1 +或0染色的病例对于基因扩增均为阴性或模棱两可。使用Ventana抗体，所有3+染色的病例均具有明确的基因扩增，但通过荧光原位杂交获得2阳性的病例均显示1+染色。用Ventana，Dako和Zymed试剂分别观察到中度（2+）H2N染色，分别为1例，3例和5例，并且与H2N基因拷贝数无关。 H2N和17号染色​​体拷贝数之间的不一致不是定义扩增的有用方法。尽管缺乏明确的基因扩增，但使用Zymed抗体的两例原位导管癌和使用Dako抗体的两例仍显示3+染色。我们得出的结论是：（1）强H2N免疫染色与基因扩增高度相关，尽管不同抗体之间的敏感性差异很小; （2）一部分子宫颈癌（3％至15％）表现出中等H2N染色而无扩增迹象，目前尚不清楚它们是否代表高度敏感的染色，还是子宫颈癌表现出未扩增而过度表达的病例; （3）通过荧光原位杂交检测到的基因扩增，每个核至少与10个基因拷贝相关，并且较低的基因拷贝重复频率（3至4 /核）是经常发生的，通常是17号染色​​体多体性的结果，而不是与高水平的过度表达有关; （5）原位导管癌中H2N过表达而不扩增可能在原位导管癌中更为常见，这意味着在浸润前肿瘤与浸润性肿瘤生物学中的作用不同。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号