ARID1A-Retained and SMARCA4-Aberrant Gastric Solid-Type Poorly Differentiated Adenocarcinoma and Prognosis: A Retrospective Cohort Study

Aims Our study investigated the clinical and pathological features of gastric solid-type poorly differentiated adenocarcinoma (PDA) along with the prognostic significance of ARID1A (AT-rich interactive domain 1A), SMARCA4, and epithelial-mesenchymal transition (EMT) markers in it. Methods We retrospectively evaluated 116 patients with primary gastric solid-type PDA, and patients were categorized according to deficient or proficient mismatch repair (MMR) status (51 and 65 patients, respectively). The expression of ARID1A, SMARCA4, and EMT markers (E-cadherin, β-catenin, vimentin, and SNAI1) was analyzed via immunohistochemistry, and the levels were assigned to the aberrant/retained or normal expression groups. The associations between the expression of ARID1A, SMARCA4, and EMT markers, clinicopathological characteristics, and prognostic impact were examined. Results Proficient MMR was associated with ARID1A-retained status ( P < .001), negative E-cadherin and β-catenin, and positive SNAI1 ( P = .033, P = .003, and P = .008, respectively) in contrast to deficient MMR. Log-rank analysis revealed that the combination of ARID1A-retained and SMARCA4-aberrant status indicated significantly lower disease-free survival and overall survival rates than ARID1A-aberrant and SMARCA4-retained group ( P < .001, P < .001, respectively). Multivariate analysis revealed that the combination of ARID1A-retained and SMARCA4-aberrant status was an independent indicator of unfavorable prognosis (hazard ratio = 4.784, P < .001). Conclusions ARID1A-retained status and expression of aberrant EMT markers (E-cadherin, β-catenin, and SNAI1) are more frequently observed in proficient-MMR in solid-type PDA. ARID1A-retained and SMARCA4-aberrant status can be considered a useful indicator of unfavorable prognosis in gastric solid-type PDA.