Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance.
Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance.
复制标题
与乳腺癌患者中的基于免疫组织化学的替代物相比，PAM50内在亚型的不一致：基因组不一致的潜在影响。
DOI：
10.4143/crt.2018.342
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发表时间：
2019-04
影响因子：
4.6
通讯作者：
Park YH
中科院分区：
文献类型：
--
作者：
Kim HK;Park KH;Kim Y;Park SE;Lee HS;Lim SW;Cho JH;Kim JY;Lee JE;Ahn JS;Im YH;Yu JH;Park YH
我们的目的是分析基于免疫组织化学（IHC）的替代亚型和PAM 50内在亚型之间的不一致性，并根据不一致性评估总生存期（OS）。共分析了607例患者。通过IHC评价激素受体（HR）表达，并通过IHC和/或荧光原位杂交分析人表皮生长因子受体2（HER2）表达。使用NanoString nCounter分析系统根据50种癌症基因确定PAM 50内在亚型。我们将一致性肿瘤匹配为管腔A和HR +/HER2-、管腔B和HR +/HER2+、HR-/HER2+和HER2富集、以及三阴性乳腺癌（TNBC）和正常或基底样。我们使用Ion Ampliseq Cancer Panel v2来鉴定与不一致性相关的基因组改变。采用Kaplan-Meier方法估计OS。共有233例患者（38.4%）在IHC基础亚型和PAM 50内在亚型之间不一致。使用靶向测序，我们检测了体细胞突变相关的不一致乳腺癌，包括HR +/HER2-组中的VHL基因（一致组中31%，不一致组中0%，p = 0.03）和TNBC组中的IDH和RET基因（分别为7% vs. 12%，p = 0.02和0% vs. 25%，p = 0.02）。在结果不一致的管腔A/B型患者中，OS显著更差（中位OS，73.6个月vs.未达到; p <0.001），在HR阳性患者中，由PAM 50确定的基底样组显示OS显著低于其他内在亚型（5年OS率，92.2% vs. 75.6%; p = 0.01）。在我们的研究中，相当一部分患者表现出IHC亚型和PAM 50内在亚型之间的差异。生存分析表明，目前基于IHC的分类可能会误导治疗并导致不良结局。目前的IHC指南可能会相应更新。
We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance. A total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2–, luminal B and HR+/HER2+, HR–/HER2+ and HER2–enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS. In total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation–related discordant breast cancer including the VHL gene in the HR+/HER2– group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01). A substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.