CHANG Kesheng 1SHAO Jin 2ZHANG Qi 1LIU Yifei2
作者信息
- 1. Department of Pathology,Wuxi Second People's Hospital,Wuxi 214002,Jiangsu Province,China
- 2. Department of Pathology,Affiliated Hospital of Nantong University,Nantong 226007,Jiangsu Province,China
- 折叠
摘要
Abstract
Background and purpose:Research on SWI/SNF chromatin remodeling complex-deficient pulmonary malignancies,particularly regarding the diagnostic criteria for distinguishing SMARCA4-deficient undifferentiated tumor(SD-UT)from poorly differentiated non-small cell lung cancer(NSCLC),remains limited.This study aimed to provide a basis for the clinical differentiation between poorly differentiated SMARCA4-deficient NSCLC and undifferentiated tumor,as well as for prognostic assessment.Methods:A retrospective analysis was conducted on patients with pulmonary malignancies who underwent surgical resection at Wuxi Second People's Hospital from 2016 to 2023,meeting the following inclusion criteria:① Histopathologically confirmed lung adenocarcinoma or undifferentiated tumor lacking any specific differentiation(squamous cell carcinoma,neuroendocrine carcinoma,etc.).② Sufficient tissue available for immunohistochemical staining and genetic testing.③ Complete follow-up data.Statistical methods included the log-rank test,Fisher's exact test,and the Wilcoxon rank-sum test.The primary endpoint was overall survival(OS),defined as the time from diagnosis to death from any cause or the last follow-up.This study was approved by the Ethics Committee of Wuxi Second People's Hospital[(2025)Ethics No.(Y-58)].Results:A total of 485 patients were enrolled,among whom 47 showed complete loss/weak positivity of SMARCA4,including 15 with well/moderately differentiated NSCLC,22 with poorly differentiated NSCLC,and 10 with UT.UT exhibited significant morphological overlap with poorly differentiated NSCLC;however,SD-UT had a higher proportion of rhabdoid tumor cells.Significant differences were observed among the 3 groups in terms of gender(male:46.67%,90.91%and 100%,P=0.002),tumor size(median diameter:2.0 cm,3.5 cm and 2.6 cm,P=0.030),and stage(proportion of stage Ⅲ-Ⅳ:0.00%,45.45%and 60.00%,P＜0.001).Survival analysis revealed no difference in survival rate between the 438 patients with SMARCA4-expressing NSCLC and the 15 patients with well/moderately differentiated SD-NSCLC.The median follow-up times for patients with well-to-moderately differentiated SD-NSCLC and poorly differentiated SD-NSCLC were 59 and 40 months,respectively.SD-UT patients were followed up for an average of 18.6 months.Patients with SD-UT(median OS was 20 months,survival rate was 0.00%)had a significantly worse prognosis than those with poorly differentiated SD-NSCLC(median OS was 56 months,survival rate was 18.52%)(P=0.022,χ2=5.252).Log-rank tests showed that,the expression of markers of AE1/AE3(positive:25 cases,negative:7 cases;P=0.022)and SMARCA2(positive:29 cases,negative:3 cases;P=0.362)were closely correlated with prognosis,while the expression of Claudin-4(positive:27 cases,negative:5 cases;P=0.561)was not significantly correlated with prognosis.Among patients with poorly differentiated SD-NSCLC and SD-UT,those who received immunotherapy showed a significant improvement in OS compared to those who did not(P=0.036).Conclusion:SMARCA4 deficiency is associated with patient gender and tumor aggressiveness.The correlation of AE1/AE3,SMARCA2,and Claudin-4 expression with prognosis provides new criteria for the classification of SMARCA4-deficient tumors.Immunotherapy demonstrates efficacy in patients with SMARCA4 deficiency.关键词
肺恶性肿瘤/SMARCA4突变/SWI/SNF复合体/预后/免疫组织化学检测Key words
Malignant lung tumor/SMARCA4 mutation/SWI/SNF complex/Prognosis/Immunohistochemistry分类
医药卫生
