SMARCA4缺失性非小细胞肺癌127例临床病理学特征及预后分析

Clinicopathological features and prognosis of SMARCA4-deficient non-small cell lung carcinoma:an analysis of 127 cases

目的:探讨SMARCA4缺失性非小细胞肺癌患者的临床病理学特点及预后。方法:收集2020年1月至2022年3月上海市肺科医院经病理确诊的SMARCA4缺失性非小细胞肺癌127例患者的临床病理学资料及预后信息,并检测治疗相关生物标志物的变异及表达情况。结果:127例SMARCA4缺失性非小细胞肺癌患者中,男性120例(94.5%),女性7例(5.5%);平均年龄63岁(年龄范围42~80岁)。临床分期Ⅰ期41例(32.3%),Ⅱ期23例(18.1%),Ⅲ期和Ⅳ期分别为31例(24.4%)和32例(25.2%)。SMARCA4免疫组织化学完全缺失表达117例(92.1%),部分缺失表达10例(7.9%);107例免疫组织化学检测PD-L1表达,PD-L1呈阴性、低表达和高表达比例分别为49.5%(53/107)、26.2%(28/107)和24.3%(26/107);靶向基因变异21例(21/104,20.2%),KRAS突变(n=10)为最常见突变类型。基因突变型SMARCA4缺失性非小细胞肺癌患者多见于女性,且与淋巴结阳性、临床分期晚相关(P<0.01)。生存分析显示临床分期晚是所有患者预后不良的影响因素,脉管阳性是手术患者疾病进展或复发的高危因素。结论:SMARCA4缺失性非小细胞肺癌是一类少见、预后差的肿瘤,常发生于老年男性患者,而伴有靶向基因变异的SMARCA4缺失性非小细胞肺癌常见于女性患者。脉管阳性是手术患者疾病进展或复发的高危因素。早发现、早治疗是改善患者预后的重要途径。

ObjectiveTo investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer.MethodsThe clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital,Shanghai,China from January 2020 to March 2022.The variation and expression of biomarkers related to treatment were retrospectively reviewed.ResultsOne hundred and twenty-seven patients were eligible for enrollment.Among them 120 patients(94.5%)were male and 7 cases(5.5%)were female,while the average age was 63 years(range 42-80 years).There were 41 cases(32.3%)of stageⅠcancer,23 cases(18.1%)of stageⅡ,31 cases(24.4%)of stageⅢand 32 cases(25.2%)of stageⅣ.SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases(92.1%)and partially absent in 10 cases(7.9%).PD-L1 immunohistochemical analyses were performed on 107 cases.PD-L1 was negative,weakly positive and strongly positive in 49.5%(53/107),26.2%(28/107)and 24.3%(26/107)of the cases,respectively.Twenty-one cases showed gene alterations(21/104,20.2%).The KRAS gene alternation(n=10)was most common.Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females,and was associated with positive lymph nodes and advanced clinical stage(P<0.01).Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor,and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection.ConclusionsSMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis,and often occurs in elderly male patients.However,SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients.Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor.Early detection and access to treatment are important for improving patient survivals.