SMARCA4 and SMARCA2 deficiency in non-small cell lung cancer: immunohistochemical survey of 316 consecutive specimens
SMARCA4 and SMARCA2 deficiency in non-small cell lung cancer: immunohistochemical survey of 316 consecutive specimens
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DOI：
10.1016/j.anndiagpath.2016.10.006
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发表时间：
2017-02-01
影响因子：
2
通讯作者：
Agaimy, Abbas
中科院分区：
文献类型：
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作者：
Herpel, Esther;Rieker, Ralf J.;Agaimy, Abbas
染色质重塑开关蔗糖不可发酵（SWI/SNF）复合物越来越多地参与肿瘤的发病和去分化，具有预后和潜在的治疗意义。在此，我们研究了SWI/SNF复合物催化亚基SMARCA4 （BRG1）和SMARCA2 （BRM）在316个连续的非小细胞肺癌（NSCLC）标本（171个腺癌[ADCAs]， 130个鳞状细胞癌[SCCs]， 9个腺鳞癌和6个大细胞癌）中组织微阵列的表达，不包括未分化/巨细胞癌或横纹肌样癌)。146例可评估肺部adca中有8例（5.5%）和115例可评估肺部SCCs中有6例（5.2%）出现SMARCA4完全缺失，而140例adca中有9例（6.4%）和117例SCCs中有2例（1.7%）出现SMARCA2缺失。6个大细胞癌中有2个存在SMARCA2缺陷。在4例（2例adca和2例SCCs）中观察到两种标记物同时丢失。在其中一种或两种标记物缺失的15例adca中，12例（80%）为TTF1阴性。总之，SMARCA4和SMARCA2缺乏症分别在5.1%和4.8%的NSCLC中观察到。所有病例中SMARCB1的表达均完整。分化组织学（腺状或鳞状）的存在是SWI/ snf缺陷癌的一个新方面，而在其他器官中，SWI/ snf缺陷癌通常与未分化/横纹肌样形态相关。TTF1阴性在SWI/ snf缺陷型肺部ADCA中占主导地位（80%），这强调了在评估TTF1阴性肺源性ADCA时需要包括这两个标志物。鉴于最近有文献表明SMARCA4缺失可能预示着NSCLC对铂类化疗的化疗敏感性，建议在常规外科病理实践中认识到缺乏SMARCA4的NSCLC的临床病理特征。(C) 2016 Elsevier Inc.版权所有。
The chromatin remodeling switch sucrose nonfermentable (SWI/SNF) complex has been increasingly implicated in the pathogenesis and dedifferentiation of neoplasms from several organs with prognostic and potential therapeutic implications. We herein investigated the expression of the SWI/SNF complex catalytic subunits SMARCA4 (BRG1) and SMARCA2 (BRM) in 316 consecutive non-small cell lung cancer (NSCLC) specimens on tissue microarrays (171 adenocarcinomas [ADCAs], 130 squamous cell carcinomas [SCCs], 9 adenosquamous carcinomas, and 6 large cell carcinomas) excluding undifferentiated/giant cell or rhabdoid carcinomas. Complete loss of SMARCA4 was observed in 8 (5.5%) of 146 evaluable pulmonary ADCAs and 6 (5.2%) of 115 evaluable pulmonary SCCs, whereas 9 (6.4%) of 140 ADCAs and 2 (1.7%) of 117 SCCs showed SMARCA2 loss. Two of 6 large cell carcinomas were SMARCA2 deficient. Concurrent loss of both markers was observed in 4 cases (2 ADCAs and 2 SCCs). Of 15 ADCAs with loss of either or both markers, 12 (80%) were TTF1 negative. In conclusion, SMARCA4 and SMARCA2 deficiency is observed in 5.1% and 4.8% of NSCLC, respectively. SMARCB1 expression was intact in all cases. The presence of differentiated histology (glandular or squamous) is a novel aspect among SWI/SNF-deficient carcinomas which in other organs generally are associated with undifferentiated/rhabdoid morphology. The predominance of TTF1 negativity among SWI/SNF-deficient pulmonary ADCA (80%) underlines the need to include these 2 markers in the evaluation of TTF1-negative ADCA of putative pulmonary origin. Given the recently documented potential of SMARCA4 loss as a predictor of chemosensitivity to platinum-based chemotherapy in NSCLC, recognition of the clinicopathological features of SMARCA4-deficient NSCLC in routine surgical pathology practice is recommended. (C) 2016 Elsevier Inc. All rights reserved.