Analysis of Clinicopathological Features in 12 Cases of BRG-1/INI-1-deficient Undifferentiated Tumors of the Digestive System
10.11714/jsysu.med.YX20260023
- VernacularTitle:12例BRG-1/INI-1缺失型消化系统未分化肿瘤临床病理特征分析
- Author:
Kaiying ZHANG
1
;
Zhengjun YANG
2
;
Yiyang ZHAO
2
;
Zhengyi QIAN
1
;
Yihong LING
2
;
Xiaoli WEI
1
Author Information
1. Department of Medical Oncology， Sun Yat-Sen University Cancer Center， Guangzhou 510060， China
2. Department of Pathology， Sun Yat-Sen University Cancer Center， Guangzhou 510060， China
- Publication Type:Journal Article
- Keywords:
BRG-1;
INI-1;
SWI/SNF complex;
undifferentiated tumor of the digestive system;
clinicopathological features
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(3):561-572
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the clinicopathological features， molecular profile， treatment response， and prognosis of SMARCA4 （BRG-1） and SMARCB1 （INI-1）-deficient undifferentiated tumors of the digestive system， aiming to enhance the understanding of this rare and highly aggressive molecular subtype. MethodsThis study is a single-center retrospective analysis. We included 9 cases of malignant digestive system tumors with loss of BRG-1 expression and 3 cases with loss of INI-1 expression， all pathologically confirmed at Sun Yat-sen University Cancer Center between April 2022 and December 2025. By reviewing clinical data， histological morphology，immunohistochemistry and next-generation sequencing （NGS） results from partial cases， we systematically summarized their clinicopathological and molecular characteristics， treatment strategies， and survival outcomes. Results Among the 12 patients， 6 were male and 6 were female， with a median age of 62 （44-70） years. 9 cases exhibited SMARCA4 deficiency， and 3 cases exhibited SMARCB1 deficiency. Tumors originated in the stomach （5 cases）， colon （3 cases）， pancreas （1 case）， with the primary site unknown in 3 cases. The histology predominantly showed undifferentiated carcinoma， with 1 case of poorly differentiated carcinoma. The tumor cells were epithelioid with significant atypia. Epithelial markers （e.g. CKpan） were often lost or markedly decreased， while vimentin could be positive. All 9 cases tested for MMR status were mismatch repair proficient （pMMR）， and the Ki-67 proliferation index was high ［median 80% （60%-90%）］. A discordance was observed between IHC findings and NGS results in the 6 sequenced cases. The NGS profiling revealed frequent co-occurring mutations， including TP53， KRAS， and NRAS， with no germline mutations identified.The median follow-up time was 277 （55-867） days. 9 of the 12 patients presented with stage Ⅳ disease at the time of initial diagnosis. Among 3 newly diagnosed patients without metastasis who received treatment， 2 achieved prolonged recurrence-free survival. Patients with advanced disease at initial diagnosis primarily underwent platinum-based chemotherapy or combination regimens， yet their prognosis was generally poor， with a median overall survival of 60 （45-541） days， ranging from 16 to 867 days. Notably， several patients who received chemotherapy combined with targeted therapy and immunotherapy achieved extended survival. ConclusionSMARCA4/SMARCB1-deficient undifferentiated tumor of the digestive system is a distinct molecular subtype characterized by high aggressiveness and poor prognosis， predominantly affecting middle-aged and elderly individuals. Diagnosis relies on the immunohistochemical loss of BRG-1 or INI-1 proteins. While no standard of care currently exists， treatment often refers to regimens for adenocarcinoma of the primary site. Combined immunotherapy and targeted therapy may offer potential benefits， warranting further validation in large-scale prospective studies.
