title: ARID1A expression in gastric adenocarcinoma: clinicopathological significance and correlation with DNA mismatch repair status.
abstract: OBJECTIVE
  To analyze the mismatch repair (MMR) status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.
  
  
  METHODS
  We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas. The results were further correlated with clinicopathological variables.
  
  
  RESULTS
  The loss of any MMR protein expression, indicative of MMR deficiency, was observed in 38 cases (7.8%) and was significantly associated with an older age (68.6±9.2 vs 60.4±11.7, P<0.001), a female sex (55.3% vs 31.3%, P=0.004), an antral location (44.7% vs 25.7%, P=0.021), and a differentiated histology (57.9% vs 39.7%, P=0.023). Abnormal ARID1A expression, including reduced or loss of ARID1A expression, was observed in 109 cases (22.3%) and was significantly correlated with lymphatic invasion (80.7% vs 69.5%, P=0.022) and lymph node metastasis (83.5% vs 73.7%, P=0.042). The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency (47.4% vs 20.2%, P<0.001). A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor (HR=1.36, 95%CI: 1.01-1.84; P=0.040).
  
  
  CONCLUSIONS
  Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion, lymph node metastasis, poor prognosis, and MMR deficiency in gastric adenocarcinomas.
authors.affiliation: Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Inada
authors.affiliation: Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.affiliation: Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katai
authors.affiliation: Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: ARID1A; Adenocarcinoma; Immunohistochemistry; Mismatch Repair; Stomach