Strong HER-2/neu protein overexpression by immunohistochemistry often does not predict oncogene amplification by fluorescence in situ hybridization
Strong HER-2/neu protein overexpression by immunohistochemistry often does not predict oncogene amplification by fluorescence in situ hybridization
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DOI：
10.1053/s0046-8177(03)00409-x
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发表时间：
2003-10-01
期刊：
影响因子：
3.3
通讯作者：
Cohen, C
中科院分区：
文献类型：
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作者：
Hammock, L;Lewis, M;Cohen, C
通过荧光原位杂交（FISH）发现HER-2/neu癌基因扩增的乳腺癌患者对曲妥珠单抗（赫赛汀）治疗的反应优于仅显示HER-2/neu蛋白过表达的患者。许多中心目前仅对通过免疫组织化学（IHC）显示2+ HER-2/neu阳性的肿瘤进行FISH，假设3+阳性实际上等同于扩增。在12个月内对102例乳腺癌病例进行的FISH结果与HER-2/neu IHC结果相关。使用HER-2/neu和染色体17着丝粒信号计数的比率进行FISH（PathVysion; Vysis，Downers格罗夫，IL）。根据HercepTest（Dako，Carpinteria，CA）公布的评分指南评价HER-2/neu的免疫组织化学表达：FISH显示，45个3+阳性肿瘤中仅22个（49%）显示扩增。25例IHC染色2+的病例中仅有2例（6%）出现基因扩增，25例IHC染色阴性的病例中有1例（4%）出现弱扩增。在25例显示癌基因扩增的病例中，22例（88%）显示3+ IHC阳性，2例（8%）显示2+ IHC阳性，1例（4%）为阴性。超过50%的乳腺肿瘤显示强3+ HER-2/neu染色不显示癌基因扩增FISH。大多数具有2+和阴性免疫组化的肿瘤也未能扩增。根据我们的经验，应在所有3+和2+染色肿瘤上进行FISH研究，以避免不适当和毒性治疗。对IHC阴性肿瘤进行FISH的决定应根据其他参数进行指导，包括肿瘤分级和雌激素受体状态。(C)2003年爱思唯尔公司All rights reserved.
Breast cancer patients with HER-2/neu oncogene amplification by fluorescence in situ hybridization (FISH) have been shown to have a better response to trastuzumab (Herceptin) therapy than those showing HER-2/neu protein overexpression only. Many centers currently perform FISH only on tumors showing 2+ HER-2/neu positivity by immunohistochemistry (IHC), with the assumption that 3+ positivity virtually equates with amplification. Results of FISH performed on 102 breast cancer cases over a 12-month period were correlated with HER-2/neu IHC results. FISH was performed using a ratio of HER-2/neu and chromosome 17 centromere signal counts (PathVysion; Vysis, Downers Grove, IL). Immunohistochemical expression of HER-2/neu was evaluated according to the published scoring guidelines of the HercepTest (Dako, Carpinteria, CA): Only 22 of 45 tumors with 3+ positivity (49%) showed amplification by FISH. Only 2 of 25 cases with 2+ staining by IHC (6%) showed gene amplification, and 1 of 25 cases with negative IHC staining (4%) showed weak amplification. Of the 25 cases showing oncogene amplification, 22 (88%) showed 3+ IHC positivity, 2 (8%) showed 2+ positivity, and 1 (4%) was negative by IHC. More than 50% of breast tumors showing strong 3+ HER-2/neu staining do not show oncogene amplification by FISH. Most tumors with 2+ and negative IHC also fail to amplify. In our experience, FISH studies should be performed on all 3+ and 2+ staining tumors to avoid inappropriate and toxic treatment. The decision to perform FISH on IHC-negative tumors should be guided by additional parameters, including tumor grade and estrogen receptor status. (C) 2003 Elsevier Inc. All rights reserved.