Loss of SWI/SNF complex expression (SMARCA4, SMARCA2, SMARCB1, ARID1A) is associated with dMMR in primary adenocarcinoma of jejunum and ileum: A clinicopathological and molecular analysis based on the Chinese population

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-03-11 DOI:10.1016/j.prp.2025.155891

Minying Deng , Rongkui Luo , Huimei Wang , Ayizimugu Abuduwaili , Dongxian Jiang , Xinyi Zhang , Lei Xu , Xiaolei Zhang , Zhiping Niu , Jieakesu Su , Chen Xu , Yingyong Hou

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引用次数: 0

Abstract

Objective

The SWI/SNF complex is an important chromatin remodeling complex that has been reported in various tumors. To date, there have been no reports on the subunits of this complex in primary small bowel adenocarcinoma (PSBA).

Methods

Hematoxylin & Eosin (H&E) staining slides were reviewed, and the expression of MMR protein, BRM (SMARCA2), BRG1 (SMARCA4), INI1 (SMARCB1), and ARID1A proteins was detected. Molecular genetic testing was performed utilizing the amplification-refractory mutation system (ARMS) and high-throughput sequencing technology.

Results

In this cohort of 58 cases, there was a trend toward a female predominance in ARID1A loss (P = 0.084), and BRM (SMARCA2) loss was associated with lymphatic invasion (P = 0.043). A significant positive correlation was observed between ARID1A loss and dMMR (P = 0.021), and BRG1 (SMARCA4) loss was more prevalent in poorly differentiated PSBA (P = 0.023). ARID1A loss was positively correlated with PIK3CA gene mutation (r = 0.551, P < 0.001), and loss of MMR protein expression was also positively correlated with PIK3CA gene mutation (r = 0.354, P = 0.006). Additionally, BRM (SMARCA2) loss showed a significant positive correlation with NRAS gene mutation (r = 0.293, P = 0.025) and a significant negative correlation with KRAS gene mutation (r = -0.281, P = 0.033). Univariate analysis indicated a trend toward poor prognosis with BRM (SMARCA2) loss (P = 0.097).

Conclusion

This study represents the initial description of loss of the SWI/SNF complex expression in PSBA, which is rare and primarily originates in the jejunum and ileum. Further investigations are warranted to elucidate potential targets of PIK3CA inhibitors for dMMR PSBA and ARID1A loss of expression in PSBA.

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SWI/SNF复合物表达缺失（SMARCA4、SMARCA2、SMARCB1、ARID1A）与原发性空肠和回肠腺癌的dMMR相关：基于中国人群的临床病理和分子分析

目的SWI/SNF复合体是一种重要的染色质重塑复合体，已在多种肿瘤中报道。到目前为止，还没有关于原发性小肠腺癌（PSBA）中该复合物亚基的报道。MethodsHematoxylin,回顾伊红（H&；E）染色切片，检测MMR蛋白、BRM （SMARCA2）、BRG1 （SMARCA4）、INI1 （SMARCB1）和ARID1A蛋白的表达。利用扩增-难解突变系统（ARMS）和高通量测序技术进行分子基因检测。结果在58例队列中，ARID1A丢失有女性优势的趋势（P = 0.084），BRM （SMARCA2）丢失与淋巴浸润相关（P = 0.043）。ARID1A缺失与dMMR之间存在显著正相关（P = 0.021），BRG1 （SMARCA4）缺失在低分化PSBA中更为普遍（P = 0.023）。ARID1A缺失与PIK3CA基因突变呈正相关（r = 0.551,P <； 0.001），MMR蛋白表达缺失与PIK3CA基因突变也呈正相关（r = 0.354,P = 0.006）。BRM （SMARCA2）缺失与NRAS基因突变呈显著正相关（r = 0.293,P = 0.025），与KRAS基因突变呈显著负相关（r = -0.281,P = 0.033）。单因素分析显示BRM （SMARCA2）丢失有预后不良的趋势（P = 0.097）。结论本研究首次描述了PSBA中SWI/SNF复合物表达的缺失，这是罕见的，主要起源于空肠和回肠。需要进一步的研究来阐明PIK3CA抑制剂对dMMR PSBA和ARID1A在PSBA中表达缺失的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.