Concordance of ATM (Ataxia Telangiectasia Mutated) Immunohistochemistry between Biopsy or Metastatic Tumor Samples and Primary Tumors in Gastric Cancer Patients
Concordance of ATM (Ataxia Telangiectasia Mutated) Immunohistochemistry between Biopsy or Metastatic Tumor Samples and Primary Tumors in Gastric Cancer Patients
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DOI：
10.1159/000346034
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发表时间：
2013-01-01
期刊：
影响因子：
5
通讯作者：
Kim, Woo Ho
中科院分区：
文献类型：
--
作者：
Kim, Hee Sung;Kim, Min A.;Kim, Woo Ho
ATM(共济失调毛细血管扩张突变)是几种DNA修复蛋白之一，当缺乏时可使肿瘤细胞对聚(ADP-核糖)聚合酶抑制剂olaparib敏感。这项研究的目的是评估胃癌ATM免疫组织化学(IHC)的时空一致性，以确定在不同样本类型和时间水平上的测量是否可能与患者水平的治疗决策相关。591例胃癌患者分为胃切除组(n=450)和转移组(n=141)，组成两个独立的队列。共检测2,705例ATM-IHC标本，包括全胃组织450例、3套450个组织芯片(TMA)、301例活检、222例转移瘤和2例全胃切除标本，以及141对原发灶和转移瘤。ATM阴性率分别为13.1%、13.9%、15.1%、16.0%和15.9%，原发灶21.4%、转移灶21.5%。活检的系数为0.341，3TMA的平均值为0.572，胃切除队列中大部分同步转移的肿瘤的系数为0.415，转移队列中的主要非同步转移肿瘤的系数为0.153。以肿瘤切除全组织切片和原发灶组织切片为参照标准，活检的特异度和敏感度分别为91.6%和41.0%，平均3次TMA的特异度和敏感度分别为93.9%和61.9%，对胃切除组转移瘤的特异度和敏感度分别为86.6%和58.8%，对转移组的特异度和敏感度分别为81.7%和33.3%。虽然我们已经证明了ATM的IHC检测方法在胃肿瘤样本中是可靠的和可重复性的，但我们也发现同一患者的多个样本类型之间的测量结果存在显著的不一致性。将需要进一步的工作，以确定是否可以通过多次抽样使分类更加一致。然而，原发转移样本和非同步转移样本之间缺乏一致性，这表明这种采样需要在任何治疗决定时进行。版权所有(C)2013 S.Karger AG，巴塞尔
ATM (ataxia telangiectasia mutated) is one of several DNA repair proteins that are suggested to sensitize tumor cells to the poly(ADP-ribose) polymerase inhibitor olaparib when deficient. The aim of this study was to assess the spatiotemporal concordance of ATM immunohistochemistry (IHC) in gastric cancer in order to determine if measurements made at the level of various sample types and times could be inferred as having the potential to be relevant to treatment decisions made at the patient level. Two independent cohorts composed of 591 gastric cancer patients divided into a gastrectomy cohort (n = 450) and a metastasis cohort (n = 141) were used in this study. A total of 2,705 ATM IHC samples were examined, including 450 whole tissue, 3 sets of 450 tissue microarray (TMA), 301 biopsy, 222 metastatic tumor and 2 additional whole tissue samples of 50 cases from the gastrectomy cohort, and 141 pairs of primary and metastatic tumors from the metastasis cohort. The prevalence of ATM negativity was 13.1% in biopsies, 13.9, 15.1, and 16.0% in TMAs and 15.9% in whole tissue samples of the gastrectomy cohort, and 21.4% in primary tumor and 21.5% in metastatic tumor samples of the metastasis cohort.. coefficients were 0.341 for biopsy, 0.572 as the average of 3 TMAs and 0.415 for the largely synchronous metastatic tumors of the gastrectomy cohort, and 0.153 for the largely asynchronous metastatic tumors of the metastasis cohort. Using whole tissue sections from tumor resections or primary tumor, respectively, as the reference standards, specificity and sensitivity were 91.6 and 41.0% for biopsy, 93.9 and 61.9% as the average of 3 TMAs, and 86.6 and 58.8% for metastatic tumors of the gastrectomy cohort and 81.7 and 33.3% for metastatic tumors of the metastasis cohort, respectively. Although we have demonstrated that the IHC assay for ATM was robust and reproducible in gastric tumor samples, we have also found that measurements were subject to significant discordance across multiple sample types from the same patient. Further work will be necessary to determine if classification may be made more consistent by multiple sampling. However, the lack of agreement between primary and asynchronous metastatic samples suggests that such sampling would need to be performed at the time of any treatment decision. Copyright (C) 2013 S. Karger AG, Basel