Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma IHC Score Algorithm for FISH
Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma IHC Score Algorithm for FISH
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DOI：
10.1097/jto.0b013e318209edb9
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发表时间：
2011-03-01
影响因子：
20.4
通讯作者：
Yang, Ping
中科院分区：
文献类型：
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作者：
Yi, Eunhee S.;Boland, Jennifer M.;Yang, Ping
需要准确、经济有效的检测间变性淋巴瘤激酶基因重排（ALK+）的方法来选择接受ALK抑制剂治疗的非小细胞肺癌患者。荧光原位杂交（FISH）用于检测ALK+，但它是昂贵的，并不是常规可用。我们探索了免疫组织化学（IHC）评分系统作为一种负担得起的、可获得的方法的潜力。方法：从梅奥诊所肺癌队列中从不吸烟的腺癌患者中获得了101个样本。采用ALK1单克隆抗体ADVANCE检测系统（Dako）和FISH双色分离探针（Abbott Molecular）对福尔马林固定石蜡包埋组织进行免疫组化检测。结果：病例的IHC评分为0（无染色，n = 69）、1+（微弱的细胞质染色，n = 21）、2+（中度，平滑的细胞质染色，n = 3）、3+（>= 10%的肿瘤细胞中强烈的颗粒状细胞质染色，n = 8）。所有IHC 3+病例为FISH+， 3例IHC 2+和21例IHC 1+中分别有1例和1例为FISH+。69例IHC 0均为FISH+。考虑到FISH是本研究的金标准参考，当2+和3+为IHC阳性，0和1+为IHC阴性时，IHC的敏感性和特异性分别为90%和97.8%。结论：IHC评分与FISH相关，可能是FISH检测非小细胞肺癌中ALK+的有用算法，类似于乳腺癌中人表皮生长因子-2的检测。需要进一步的研究来验证这种方法。
Introduction: Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach.Methods: One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue.Results: Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in >= 10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH+. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative.Conclusions: IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.