SMARCA4缺失性肺腺癌25例临床病理特征分析OA

Objective To investigate the clinicopathological and molecular genetic characteristics of SMARCA4-deficient lung adenocarcinoma.Methods A total of 25 cases were collected.Histological examination,immunohisto-chemical staining,and follow-up analysis were performed.Among them,4 cases with clear cell morphology and 1 case with partial loss of both BRG1 and INI1 were selected for next-generation sequencing(NGS).Results The co-hort was predominantly male(23/25),with an age range of 42-70 years(median:60 years).Histologically,the tu-mors mainly exhibited solid growth patterns,with focal areas showing complex glandular,cribriform,and micropapil-lary architectures.Tumor cells demonstrated moderate to severe nuclear atypia and pathological mitotic figures were observed.Immunohistochemically,CK7 was positive in 21/25 cases,TTF-1 in 11/25,and Napsin A in 9/25.All cases showed diffuse membranous positivity for CKpan,while p40 and SALL4 were negative in all cases.BRG1 ex-pression was completely lost in 88.0%(22/25)of cases and partially lost in 12.0%(3/25).INI1 expression was re-tained in 84.0%(21/25)of cases,while concurrent partial loss of BRG1 and INI1 was observed in 16.0%(4/25).NGS identified SMARCA4 mutations in 4 cases(one deletion mutation and three point mutations),including 1 case with a coexisting ARID1A mutation and one with a concurrent SMARCA2 mutation.Other mutations included KRAS(2/5),TP53(3/5),EGFR(1/5),and RB1(1/5).All 5 sequenced cases were microsatellite stable.Follow-up data were available for 20 patients,with a median follow-up period of 18-140 months.Among them,5 died,13 experi-enced disease progression,and 2 remained alive with stable disease.Conclusion SMARCA4-deficient lung adeno-carcinoma exhibits diverse histological features and frequently expresses CK7.Routine BRG1 immunohistochemical testing is recommended in poorly differentiated lung adenocarcinomas to improve prognostic assessment and guide treat-ment strategies.