[Gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype: a clinicopathological and molecular analysis].

Objective: To investigate the clinicopathological features and molecular genetic characteristics of gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype. Methods: Six cases of gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype diagnosed at the Henan Cancer Hospital, Zhengzhou, China from January 2019 to December 2021 were collected. Histological observation, immunohistochemical staining, next-generation sequencing, and detection of mismatch repair (MMR), EBER, and HER2 were performed. The clinicopathological and molecular characteristics were summarized and relevant literatures were reviewed. Results: The 6 patients were all male, aged 48-75 years. Their initial symptoms mainly included abdominal pain, melena, and dysphagia. Endoscopic examinations showed gastric ulcer type masses, and the morphology of H&E were similar: the tumor cells showed diffuse infiltrating growth, no specific structural characteristics, obvious cell atypia, obvious mitoses, and rhabdomyoid cells with unequal proportions of eosinophilic cytoplasm. The immunohistochemistry for CKpan was negative in 3 of the 6 cases, while focal expression of other epithelial markers was found, including EMA (6/6), CK8/18 (4/6), and CK7 (1/6). P53 was diffusely strong positive in 4 cases (4/6), and negative in 1 case (1/6). Ki-67 was highly expressed (positive rate range, 60%-90%). Other related markers such as mesenchymal tumors, lymphoma, melanoma and germ cell tumors were all negative. Detection of the SWI/SNF complex subunit, namely INI1 (SMARCB1), BRG1 (SMARCA4), ARID1A protein detection, was detected in 5 cases with no SMARCA4 expression (5/6), 1 case with no ARID1A expression (1/6), and all cases with SMARCB1 expression (6/6). MMR proteins were examined, and dMMR was found in 1 of the 6 cases. HER2 expression was 0 in 3 cases, 1+ in 1 case, and 2+ in 2 cases, while no amplifications of HER2 gene were detected using FISH. EBER was negative in all 6 cases. Among the 4 cases of surgical radical treatment that were subject to next-generation sequencing, 3 cases showed TP53 mutations; 1 case showed ARID1A gene frame shift mutation, and there were also mutations of ATM, PTEN and other genes. There was 1 case with detected SMARCA4 gene copy number variant, and other gene mutations such as ALK, BRAF, CDKN1B, BRCA2, etc. Conclusions: Gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype is a poorly differentiated and rare tumor. Detection of SWI/SNF complex related proteins is helpful for its diagnosis. Moreover, gene mutations associated with SWI/SNF complex will become a new indicator for its diagnosis and prognostication, and a potential new target for molecular therapy, which deserves more attention and warrants more research.目的： 探讨胃SWI/SNF复合体缺失的伴横纹肌样特征未分化癌的临床病理学和分子遗传学特征。 方法： 收集河南省肿瘤医院2019年1月至2021年12月诊断胃SWI/SNF复合体缺失的伴横纹肌样特征未分化癌6例，对其进行组织学观察、免疫组织化学染色及二代测序，并行错配修复（MMR）蛋白、EB病毒编码的RNA（EBER）、HER2检测，总结其临床病理及分子特点，进行相关文献复习。 结果： 6例患者均为男性，年龄48~75岁，首发症状主要为腹痛、黑便、吞咽不利，内镜提示胃部溃疡型肿物，镜下形态相似：肿瘤细胞呈弥漫浸润性生长，细胞异型性明显，核分裂象易见，并可见到比例不等的丰富嗜酸性胞质呈横纹肌样形态细胞。免疫组织化学3例广谱细胞角蛋白（CKpan）为阴性，但其他上皮标志物如上皮细胞膜抗原（EMA，6/6）、细胞角蛋白（CK）8/18（4/6）、CK7（1/6）可见灶性区阳性表达；p53蛋白4例弥漫强阳性（4/6），1例为阴性（1/6）；Ki-67阳性指数60%~90%。其他间叶源性肿瘤、淋巴造血系统肿瘤、色素细胞肿瘤、生殖细胞肿瘤等相关标志物均为阴性表达。SWI/SNF复合体亚基检测，即INI1（SMARCB1）、BRG1（SMARCA4）、ARID1A蛋白检测，5例为SMARCA4缺失表达（5/6），1例为ARID1A缺失表达（1/6），所有病例SMARCB1均未缺失；进行MMR检测，其中1例为MMR缺陷。3例HER2表达为0（3/6），1例为1+（1/6），2例为2+（2/6），行荧光原位杂交（FISH）检测HER2基因均无扩增；6例患者EBER均为阴性。4例手术根治标本行二代测序，3例检测到TP53突变（3/4），1例检测到ARID1A基因移码缺失突变，同时存在ATM、PTEN等突变，1例检测到SMARCA4基因拷贝数变异，同时存在ALK、BRAF、CDKN1B、BRCA2等基因突变。 结论： 胃SWI/SNF复合体缺失的伴横纹肌样特征未分化癌是一种分化极差且罕见的肿瘤，进行SWI/SNF复合体相关蛋白检测有助于诊断，与SWI/SNF复合体相关的基因改变将成为以后诊断、预后评估的新指标以及潜在的分子治疗新靶点，值得进一步关注。.