Herpel Esther, Rieker Ralf J, Dienemann Hendrik, Muley Thomas, Meister Michael, Hartmann Arndt, Warth Arne, Agaimy Abbas
Institute of Pathology, University Hospital of Heidelberg, Heidelberg, Germany.
Institute of Pathology, University Hospital of Erlangen, Erlangen, Germany.
Ann Diagn Pathol. 2017 Feb;26:47-51. doi: 10.1016/j.anndiagpath.2016.10.006. Epub 2016 Oct 20.
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.
染色质重塑开关蔗糖非发酵型（SWI/SNF）复合物越来越多地与多个器官肿瘤的发病机制和去分化相关，具有预后和潜在治疗意义。我们在此研究了SWI/SNF复合物催化亚基SMARCA4（BRG1）和SMARCA2（BRM）在组织芯片上316例连续非小细胞肺癌（NSCLC）标本中的表达情况（171例腺癌[ADCA]、130例鳞状细胞癌[SCC]、9例腺鳞癌和6例大细胞癌），排除未分化/巨细胞癌或横纹肌样癌。在146例可评估的肺ADCA中有8例（5.5%）和115例可评估的肺SCC中有6例（5.2%）观察到SMARCA4完全缺失，而在140例ADCA中有9例（6.4%）和117例SCC中有2例（1.7%）出现SMARCA2缺失。6例大细胞癌中有2例存在SMARCA2缺陷。4例（2例ADCA和2例SCC）观察到两种标志物同时缺失。在15例缺失一种或两种标志物的ADCA中，12例（80%）TTF1阴性。总之，NSCLC中分别有5.1%和4.8%观察到SMARCA4和SMARCA2缺陷。所有病例中SMARCB1表达均完整。分化组织学（腺性或鳞状）的存在是SWI/SNF缺陷型癌的一个新特征，在其他器官中通常与未分化/横纹肌样形态相关。SWI/SNF缺陷型肺ADCA中TTF1阴性占优势（80%），这突出了在评估疑似肺源性TTF1阴性ADCA时纳入这两种标志物的必要性。鉴于最近有文献报道SMARCA4缺失可能是NSCLC对铂类化疗药物敏感性的预测指标，建议在常规外科病理实践中认识SMARCA4缺陷型NSCLC的临床病理特征。
