Abstract
Undifferentiated gastric carcinoma, characterized by anaplastic cells lacking distinct features of cytological or architectural differentiation, poses diagnostic and therapeutic challenges. Recent studies have suggested an association between this carcinoma and deficiencies in the SWI/SNF complex, particularly mutations in subunits such as SMARCA4. We herein report six cases of SMARCA4-deficient undifferentiated gastric carcinoma with molecular findings, highlighting the rarity and diagnostic pitfalls of this malignancy. Predominantly occurring in males over 50 years, these cases presented with nonspecific symptoms and were often diagnosed at an advanced stage. Histologically, the tumors exhibited a sheet-like growth pattern, reduced or absent epithelial markers, and loss of BRG-1 expression, with molecular analysis confirming SMARCA4 gene mutations. The response to conventional chemotherapy was poor, underscoring the importance of complete surgical resection and the development of alternative treatment modalities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182–8.
Agaimy A, Rau TT, Hartmann A, Stoehr R. SMARCB1 (INI1)-negative rhabdoid carcinomas of the gastrointestinal tract: clinicopathologic and molecular study of a highly aggressive variant with literature review. Am J Surg Pathol. 2014;38:910–20.
Zhang Z, Li Q, Sun S, et al. Clinicopathological and prognostic significance of SWI/SNF complex subunits in undifferentiated gastric carcinoma. World J Surg Oncol. 2022;20:383.
Mittal P, Roberts CWM. The SWI/SNF complex in cancer—biology, biomarkers and therapy. Nat Rev Clin Oncol. 2020;17:435–48.
Agaimy A, Daum O, Märkl B, Lichtmannegger I, Michal M, Hartmann A. SWI/SNF complex-deficient undifferentiated/rhabdoid carcinomas of the gastrointestinal tract: a series of 13 cases highlighting mutually exclusive loss of SMARCA4 and SMARCA2 and frequent co-inactivation of SMARCB1 and SMARCA2. Am J Surg Pathol. 2016;40:544–53.
Chang B, Sheng W, Wang L, et al. SWI/SNF complex-deficient undifferentiated carcinoma of the gastrointestinal tract: clinicopathologic study of 30 cases with an emphasis on variable morphology, immune features, and the prognostic significance of different SMARCA4 and SMARCA2 subunit deficiencies. Am J Surg Pathol. 2022;46:889–906.
Mardinian K, Adashek JJ, Botta GP, Kato S, Kurzrock R. SMARCA4: implications of an altered chromatin-remodeling gene for cancer development and therapy. Mol Cancer Ther. 2021;20:2341–51.
Kim JE, Chun SM, Hong YS, et al. Mutation burden and i index for detection of microsatellite instability in colorectal cancer by targeted next-generation sequencing. J Mol Diagn. 2019;21:241–50.
Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS ONE. 2013;8: e55119.
Witkowski L, Goudie C, Ramos P, et al. The influence of clinical and genetic factors on patient outcome in small cell carcinoma of the ovary, hypercalcemic type. Gynecol Oncol. 2016;141:454–60.
Le Loarer F, Watson S, Pierron G, et al. SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. Nat Genet. 2015;47:1200–5.
Neil AJ, Zhao L, Isidro RA, Srivastava A, Cleary JM, Dong F. SMARCA4 mutations in carcinomas of the esophagus, esophagogastric junction, and stomach. Mod Pathol. 2023;36: 100183.
Huang SC, Ng KF, Yeh TS, et al. The clinicopathological and molecular analysis of gastric cancer with altered SMARCA4 expression. Histopathology. 2020;77:250–61.
Karanian-Philippe M, Velasco V, Longy M, et al. SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas. Am J Surg Pathol. 2015;39:1197–205.
Zhang Z, Li Q, Sun S, et al. Expression of SMARCA2 and SMARCA4 in gastric adenocarcinoma and construction of a nomogram prognostic model. Int J Clin Oncol. 2023;28:1487–500.
Author information
Authors and Affiliations
Contributions
Conceptualization: YSP, HRA; data acquisition: YSP, HDK, HRA; funding acquisition: HDK; supervision: YSP, HDK, MHR; writing—original draft: HRA; writing—review and editing: YSP, HDK, MHR. All authors approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
No potential conflicts of interest relevant to this article were reported. During this work, MHR received honoraria from DAEHWA Pharmaceuticals, Bristol Myers Squibb, Lilly, Ono Pharmaceuticals, MSD, Taiho Pharmaceuticals, Novartis, Daiichi Sankyo, and AstraZeneca; and served as a consultant for DAEHWA Pharmaceuticals, Bristol Myers Squibb, Lilly and Ono Pharmaceuticals. HDK received honoraria from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceuticals, Boryung Pharmaceuticals, MSD, Daiichi Sankyo, and Boostimmune; received research grants from AstraZeneca and Roche/Genentech; and served as a consultant for Mustbio.
Ethical approval
This report was approved by the Institutional Review Board of the Asan Medical Center (AMC 2024–0228).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
An, H.R., Kim, HD., Ryu, MH. et al. SMARCA4-deficient undifferentiated gastric carcinoma: a case series and literature review. Gastric Cancer (2024). https://doi.org/10.1007/s10120-024-01510-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10120-024-01510-9