Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Cancer Med. 2024 Jan;13(1):e6809. doi: 10.1002/cam4.6809. Epub 2023 Dec 20.
SMARCA4-deficient thoracic tumors, characterized by distinct clinicopathological, morphological, immunohistochemical, and genetic features, differ significantly from conventional non-small-cell lung carcinomas (NSCLCs). This group encompasses both SMARCA4-deficient NSCLCs (SMARCA4-NSCLCs) and SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs). The efficacy of PD-1 inhibitors in treating SMARCA4-deficient thoracic tumors remains uncertain.
Medical records of 36 patients diagnosed with stage IIIB, IIIC, or IV SMARCA4-deficient thoracic tumors were analyzed. We assessed the clinical, pathological, and genetic features of these patients through immunohistochemistry (IHC) and a 68-gene panel next-generation sequencing (NGS). We compared the differences between SMARCA4-NSCLCs and SMARCA4-UTs, and evaluated the impact of chemotherapy and immunotherapy on patient outcomes.
The majority of patients with SMARCA4-deficient thoracic tumors were heavy-smoking males, averaging 64.6 years in age. IHC predominantly showed weak or negative staining for markers such as TTF-1, CK5/6, p40, synaptophysin, chromogranin A, and CD56, which are often associated with adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors. The most common genetic mutations identified via NGS included TP53, CDKN2A, KRAS, STK11, NF1, and PTEN. No significant overall survival (OS) difference was observed between SMARCA4-NSCLCs and SMARCA4-UTs (p = 0.366). The median OS for patients treated with chemotherapy (n = 9) was 447 days, while the median OS for patients undergoing PD-1-inhibitor-based therapy (n = 16) was not reached (p = 0.105).
SMARCA4-deficient thoracic tumors exhibit distinct characteristics from conventional NSCLCs, and PD-1 inhibitors show promise in treating advanced SMARCA4-deficient thoracic tumors.
SMARCA4 缺陷型胸内肿瘤具有独特的临床病理、形态学、免疫组化和遗传学特征，与传统的非小细胞肺癌（NSCLC）有显著差异。这组肿瘤包括 SMARCA4 缺陷型 NSCLC（SMARCA4-NSCLC）和 SMARCA4 缺陷型未分化肿瘤（SMARCA4-UT）。PD-1 抑制剂治疗 SMARCA4 缺陷型胸内肿瘤的疗效尚不确定。
分析了 36 例 IIIB 期、IIIC 期或 IV 期 SMARCA4 缺陷型胸内肿瘤患者的病历。我们通过免疫组化（IHC）和 68 基因 panel 下一代测序（NGS）评估这些患者的临床、病理和遗传学特征。我们比较了 SMARCA4-NSCLC 和 SMARCA4-UT 之间的差异，并评估了化疗和免疫治疗对患者结局的影响。
大多数 SMARCA4 缺陷型胸内肿瘤患者为重度吸烟男性，平均年龄为 64.6 岁。IHC 主要显示 TTF-1、CK5/6、p40、突触素、嗜铬粒蛋白 A 和 CD56 等标志物的弱或阴性染色，这些标志物通常与腺癌、鳞状细胞癌和神经内分泌肿瘤有关。通过 NGS 确定的最常见基因突变包括 TP53、CDKN2A、KRAS、STK11、NF1 和 PTEN。SMARCA4-NSCLC 和 SMARCA4-UT 之间的总生存期（OS）无显著差异（p=0.366）。接受化疗（n=9）的患者中位 OS 为 447 天，而接受 PD-1 抑制剂治疗（n=16）的患者中位 OS 未达到（p=0.105）。
SMARCA4 缺陷型胸内肿瘤具有与传统 NSCLC 不同的特征，PD-1 抑制剂有望治疗晚期 SMARCA4 缺陷型胸内肿瘤。
