title: RHOA mutation in diffuse-type gastric cancer: a comparative clinicopathology analysis of 87 cases.
abstract: BACKGROUND
  Recent studies have discovered recurrent RHOA mutations in diffuse-type gastric cancers. These reports show mutant RhoA is an important cancer driver and is a potential therapeutic target. This study aims to investigate the clinicopathological features of diffuse-type gastric cancers with RHOA mutation.
  
  
  METHODS
  We performed a thorough review of 87 diffuse-type gastric cancers, including 22 RHOA-mutated and 65 RHOA wild-type gastric cancers.
  
  
  RESULTS
  Most advanced tumors with RHOA mutation appeared as Borrmann type 3 lesions (81 %) developing in the middle (50 %) or distal (32 %) third of the stomach. Histologically, although all of the tumors were predominantly or exclusively composed of poorly cohesive carcinoma, limited tubular differentiation was also observed in 73 % of the RHOA-mutated tumors. Notably, RHOA-mutated tumors more frequently showed a permeative growth pattern at the edge of the mucosal area (59 %) compared with RHOA wild-type tumors (29 %, P = 0.0202). Additionally, the size ratios of the deeply invasive components to the mucosal components were significantly lower in RHOA-mutated tumors [less than 1.45 (median) in 68 % of cases] than in RHOA wild-type tumors (less than 1.45 in 42 % of cases, P = 0.0482). RHOA mutation did not significantly impact survival in this study.
  
  
  CONCLUSIONS
  These observations suggest that RHOA mutation may be associated with the growth patterns of diffuse-type gastric cancer but have a limited prognostic impact in isolation. Further studies, including analyses of the other alterations involving the RhoA pathways, such as CLDN18-ARHGAP fusion, as well as functional studies of mutant RhoA, are necessary to clarify the significance of alterations in the RhoA-signaling pathway in diffuse-type gastric cancers.
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ushiku
authors.affiliation: Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. sish.gpat@mri.tmd.ac.jp.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.|Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Kakiuchi
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Department of Pathology, Massachusetts General Hospital Boston, Boston, MA, USA.
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein
keywords: Diffuse type; Gastric cancer; Mutation; RHOA
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