title: Various ARID1A expression patterns and their clinical significance in gastric cancers.
abstract: AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancers, and loss of ARID1A expression is considered a poor prognostic factor in various cancers. However, in practice, ARID1A shows various expression patterns, and our understanding of its significance is limited. We performed immunohistochemistry for ARID1A, MLH1, and pS6 using whole tissue blocks of 350 gastric cancers and classified the ARID1A expression as follows: retained (63.7%), reduced (17.7%), complete loss (14.9%), and partial loss (3.7%). Complete/partial loss was more common in poorly differentiated histology (P < .001), and reduced or complete loss of ARID1A was frequent in cases with MLH1 loss (P < .001). The ARID1A-reduced group showed only slightly inferior disease-free survival (DFS; P = .254) and overall survival (OS; P = .377) compared to those of the ARID1A-retained group, whereas the group with complete loss showed significantly worse DFS (hazard ratio [HR], 1.732; P = .015) and OS (HR, 1.751; P = .013). Worse DFS (HR, 2.672; P = .005) and OS (HR, 2.531; P = .002) were also noted in the group with partial loss. High expression of pS6 was observed more frequently in groups showing altered ARID1A expression patterns (P < .001). In conclusion, reduced ARID1A expression is not a major prognostic determinant, although it may lead to AKT pathway activation. Tumor cells lacking ARID1A expression may influence the prognosis even if they constitute only a small proportion of the tumor sample. Our data provide an enhanced roadmap for understanding ARID1A with implications for future research and therapeutics.
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon 443-380, Republic of Korea.
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Surgery, Ajou University School of Medicine, Suwon 443-380, Republic of Korea.
authors.forename: In-Hye
authors.initials: IH
authors.lastname: Ham
authors.affiliation: Department of Surgery, Ajou University School of Medicine, Suwon 443-380, Republic of Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Hur
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon 443-380, Republic of Korea. Electronic address: dakeun@gmail.com.
authors.forename: Dakeun
authors.initials: D
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D019893:Ribosomal Protein S6 Kinases / Q000032:analysis; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C112476:ARID1A protein, human; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D019893:Ribosomal Protein S6 Kinases; D000070957:MutL Protein Homolog 1
keywords: AKT pathway; ARID1A; Gastric cancer; Immunohistochemistry; Prognosis