Original Article

The clinicopathological and molecular analysis of gastric cancer with altered SMARCA4 expression

Shih-Chiang Huang

orcid.org/0000-0002-5092-4434

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

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Kwai-Fong Ng,

Kwai-Fong Ng

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Ta-Sen Yeh,

Ta-Sen Yeh

Department of Surgery, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Chi-Tung Cheng,

Chi-Tung Cheng

Department of Surgery, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Min-Chi Chen,

Min-Chi Chen

Department of Public Health, College of Medicine, Biostatistics Consulting Center, Chang Gung University, Taoyuan, Taiwan

Department of Hematology and Oncology, College of Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung University, Chiayi, Taiwan

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Yi-Chun Chao,

Yi-Chun Chao

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Huei-Chieh Chuang,

Huei-Chieh Chuang

Department of Anatomic Pathology, College of Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung University, Chiayi, Taiwan

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Yu-Jen Liu,

Yu-Jen Liu

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Tse-Ching Chen,

Corresponding Author

Tse-Ching Chen

[email protected]

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

Address for correspondence: Tse-Ching Chen MD, PhD, Department of Anatomic Pathology, Chang Gung Memorial Hospital, No. 5, Fuxing Street, Guishan District, Taoyuan City 33305, Taiwan. e-mail: [email protected]

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Shih-Chiang Huang,

Shih-Chiang Huang

orcid.org/0000-0002-5092-4434

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

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Kwai-Fong Ng,

Kwai-Fong Ng

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Ta-Sen Yeh,

Ta-Sen Yeh

Department of Surgery, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Chi-Tung Cheng,

Chi-Tung Cheng

Department of Surgery, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Min-Chi Chen,

Min-Chi Chen

Department of Public Health, College of Medicine, Biostatistics Consulting Center, Chang Gung University, Taoyuan, Taiwan

Department of Hematology and Oncology, College of Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung University, Chiayi, Taiwan

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Yi-Chun Chao,

Yi-Chun Chao

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Huei-Chieh Chuang,

Huei-Chieh Chuang

Department of Anatomic Pathology, College of Medicine, Chiayi Chang Gung Memorial Hospital, Chang Gung University, Chiayi, Taiwan

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Yu-Jen Liu,

Yu-Jen Liu

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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Tse-Ching Chen,

Corresponding Author

Tse-Ching Chen

[email protected]

Department of Anatomic Pathology, College of Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

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First published: 28 April 2020

https://doi.org/10.1111/his.14117

Citations: 34

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Abstract

Aims

In this study, we examine the clinicopathological and molecular features of gastric cancer (GC) with SMARCA4 alterations.

Methods and results

We screened SMARCA4 alterations using immunohistochemistry on 1199 surgically resected GCs with information on Epstein–Barr virus (EBV), microsatellite instability (MSI) and other SWI/SNF subunits. SMARCA4, SMARCA2 and ARID1A mutations were investigated by targeted sequencing. The clinicopathological significance was determined by statistical analysis. Twenty-seven cases (2%) with altered SMARCA4 expression were identified, exhibiting completely lost (six), reduced (nine) or heterogeneous (12) patterns. Frequent concomitant alterations of other SWI/SNF subunits were noted with an unusual discordant spatial heterogeneity. In comparison with SMARCA4-retained GCs, SMARCA4-lost GCs were observed more frequently in the non-EBV/MSI subgroup (five of six) and reduced or heterogeneous SMARCA4 expression mainly occurred in EBV- or MSI-associated cases (six of nine and six of 12, respectively; P < 0.001). Histologically, SMARCA4-altered GC, irrespective of expression pattern, demonstrated divergent histomorphology, spanning tubular, poorly cohesive or mixed, neuroendocrine to solid and undifferentiated carcinoma, with a predilection to the latter two (P < 0.001). De-differentiation-like transition and rhabdoid features were noted in a minority of cases. For overall survival, altered SMARCA4 expression was an unfavourable prognostic factor in stage III, EBV-associated GC and non-EBV/MSI intestinal subtype (P ≤ 0.001). SMARCA4 or ARID1A mutations were detected mainly in SMARCA4-lost or reduced GC, respectively.

Conclusions

SMARCA4-altered GCs are rare and have intratumoral heterogeneity, histomorphological diversity, conditional prognostic significance and various genetic drivers. SMARCA4-lost GC may represent a genuine SMARCA4-deficient neoplasm, but most SMARCA4-reduced/heterogeneous cases are secondary to ARID1A collapse or associated with different genotypes.

Conflicts of interest

The authors declare no conflicts of interest.

Supporting Information

References

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Citing Literature

Volume77, Issue2

The Histopathology of COVID‐19

August 2020

Pages 250-261

Filename	Description
his14117-sup-0001-TableS1.docxWord document, 36.1 KB	Table S1. The clinicopathological differences between SMARCA4-retained and SMARCA4-altered gastric cancers.
his14117-sup-0002-TableS2.docxWord document, 36.6 KB	Table S2. The clinicopathological features of gastric cancer divided by the patterns of SMARCA4 alteration.

The clinicopathological and molecular analysis of gastric cancer with altered SMARCA4 expression

Abstract

Aims

Methods and results

Conclusions

Conflicts of interest

Supporting Information

References

Citing Literature

References

Information

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The clinicopathological and molecular analysis of gastric cancer with altered SMARCA4 expression

Abstract

Aims

Methods and results

Conclusions

Conflicts of interest

Supporting Information

References

Citing Literature

References

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