目的:BRG1缺陷型NSCLC最近因其高度侵袭性的临床行为和没有有效的治疗方法而更吸引人。这项研究表征了BRG1缺陷型NSCLC的临床和病理特征,并调查了它们对免疫疗法的反应。
方法:纳入47例BRG1缺陷型NSCLC患者。免疫组织化学标志物如BRG1、CK7、TTF-1、NapsinA、P40,HepPar-1,Ki-67,BRM,ARID1A和ARID1B染色。此外,PD-L1表达水平,总生存率,评估接受免疫治疗的患者的无进展生存期和疾病控制率.
结果:这项研究表明:(1)BRG1缺陷型NSCLC患者的男性优势(89.4%),吸烟者富集(76.6%)和不良预后(中位OS:晚期7.0个月)。(2)组织学,BRG1缺陷型NSCLCs表现出显着的形态多样性,没有瘦素模式。炎性浸润和肿瘤坏死是一个突出的特征。免疫组织化学分析显示,60.9%(28/46)的病例具有独特的统一免疫表型(TTF-1-/NapsinA-/CK7),46.5%(20/43)的病例具有HepPar-1阳性。11.8%(4/34)的病例同时存在BRM丢失或显著减少。没有病例(0/37)显示ARID1A或ARID1B丢失。(3)8例晚期肿瘤患者接受了免疫治疗,4例获得了可持续的临床缓解,疾病控制率为50%。
结论:BRG1缺陷型NSCLC表现出不同的组织病理学模式和独特的免疫组织化学表型。基于ICIs的免疫疗法是一种有前途的疗法,需要进一步研究BRG1缺陷型NSCLC。
OBJECTIVE: BRG1-deficient NSCLCs have been more intriguing recently for its highly aggressive clinical behavior and no effective therapies. This study characterized the clinical and pathological features of BRG1-deficient NSCLCs and investigated their response to immunotherapy.
METHODS: Forty-seven cases with BRG1-deficient NSCLC were included. Immunohistochemical markers such as BRG1, CK7, TTF-1, NapsinA, P40, HepPar-1, Ki-67, BRM, ARID1A and ARID1B were stained. Additionally, the PD-L1 expression level, overall survival, progression-free survival and disease control rate of patients received immunotherapy were evaluated.
RESULTS: This study revealed that: (1) Patients with BRG1-deficient NSCLC have a male predominance (89.4 %), smoker enrichment (76.6 %) and poor prognosis (median OS: 7.0 months for advanced stage). (2) Histologically, BRG1-deficient NSCLCs presented significant morphological diversity and no lepidic pattern. Inflammatory infiltration and tumor necrosis was a prominent feature. Immunohistochemical analyses showed a distinctive uniform immunophenotype (TTF-1-/NapsinA-/CK7+) in 60.9 % (28/46) of cases and HepPar-1 positive in 46.5 % (20/43) of cases. BRM loss or significant reduction coexisted in 11.8 % (4/34) of cases. No case (0/37) showed loss of ARID1A or ARID1B. (3) Eight patients with advanced tumor stage had received immunotherapy and 4 cases achieved a sustainable clinical response with the disease control rate of 50 %.
CONCLUSIONS: BRG1-deficient NSCLC showed diverse histopathological patterns and a unique immunohistochemical phenotype. ICIs-based immunotherapy is a promising therapy needs to be investigated further for BRG1- deficient NSCLC.