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Updated: Jun 23, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT): a clinicopathological analysis of four rare cases
Ping Zhou1, Yiyun Fu1, Weiya Wang1
1Department of Pathology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, P.R. China.
Background:
SMARCA4, as one of the subunits of the SWI/SNF chromatin remodeling complex, drives SMARCA4-deficient tumors. Gastric SMARCA4-deficient tumors may include gastric SMARCA4-deficient carcinoma and gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Gastric SMARCA4-UT is rare and challenging to diagnose in clinical practice. The present report aims to provide insight into the clinicopathological characteristics and genetic alterations of gastric SMARCA4-UTs.
Results:
We retrospectively reported four rare cases of gastric SMARCA4-UTs. All four cases were male, aged between 61 and 82 years. These tumors presented as ulcerated and transmural masses with infiltration, staged as TNM IV in cases 1, 2 and 4, and TNM IIIA in case 3. Pathologically, four cases presented solid architecture with undifferentiated morphology. Cases 2 and 3 showed focal necrosis and focal rhabdoid morphology. Immunohistochemical staining showed negative expression of epithelial markers and deficient expression of SMARCA4. Furthermore, positivity for Syn (cases 1, 2 and 3) and SALL4 (cases 1 and 2) were observed. Mutant p53 expression occurred in four cases, resulting in strong and diffuse staining of p53 expression in cases 1, 2 and 4, and complete loss in case 3. The Ki67 proliferative index exceeded 80%. 25% (1/4, case 4) of cases had mismatch repair deficiency (dMMR). Two available cases (cases 1 and 3) were detected with SMRACA4 gene alterations. The response to neoadjuvant therapy was ineffective in case 1.
Conclusions:
Gastric SMARCA4-UT is a rare entity of gastric cancer with a poor prognosis, predominantly occurs in male patients. The tumors are typically diagnosed at advanced stages and shows a solid architecture with undifferentiated morphology. Negative expression of epithelial markers and complete loss of SMARCA4 immunoexpression are emerging as a useful diagnostic tool for rare gastric SMARCA4-UTs.
Insights
Gastric SMARCA4-UT is a rare, aggressive cancer primarily affecting males, often diagnosed at advanced stages. Loss of SMARCA4 expression and undifferentiated morphology are key diagnostic features.
Area of Science:
- Oncology
- Gastroenterology
- Pathology
Background:
- SMARCA4-deficient tumors, including gastric SMARCA4-deficient undifferentiated tumors (SMARCA4-UT), are driven by SMARCA4 subunit mutations within the SWI/SNF chromatin remodeling complex.
- Gastric SMARCA4-UT is a rare and diagnostically challenging entity within gastric cancers.
Purpose of the Study:
- To investigate the clinicopathological characteristics of gastric SMARCA4-UT.
- To identify genetic alterations associated with gastric SMARCA4-UT.
Main Methods:
- Retrospective analysis of four rare cases of gastric SMARCA4-UT.
- Evaluation of clinicopathological features, including tumor morphology, staging, and immunohistochemical markers (epithelial markers, SMARCA4, Syn, SALL4, p53, Ki67).
- Assessment of mismatch repair deficiency (dMMR) and SMARCA4 gene alterations.
Main Results:
- All four cases were male, aged 61-82, presenting as advanced-stage (TNM IV or IIIA) ulcerated, transmural masses.
- Pathological findings included solid architecture, undifferentiated morphology, focal necrosis, and rhabdoid features in some cases.
- Immunohistochemistry revealed negative epithelial markers, deficient SMARCA4 expression, positivity for Syn and SALL4 in some cases, mutant p53 expression in all cases, and a high Ki67 index (>80%). One case (25%) showed dMMR, and two cases had SMARCA4 gene alterations. Neoadjuvant therapy was ineffective in one case.
Conclusions:
- Gastric SMARCA4-UT is a rare gastric cancer subtype with a poor prognosis, predominantly affecting males and diagnosed at advanced stages.
- The tumors exhibit a solid, undifferentiated morphology.
- Negative epithelial marker expression and loss of SMARCA4 immunoexpression are valuable diagnostic indicators for this rare entity.
