論文

査読有り
2016年4月

RHOA mutation in diffuse-type gastric cancer: a comparative clinicopathology analysis of 87 cases.

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
  • Tetsuo Ushiku
  • ,
  • Shumpei Ishikawa
  • ,
  • Miwako Kakiuchi
  • ,
  • Atsushi Tanaka
  • ,
  • Hiroto Katoh
  • ,
  • Hiroyuki Aburatani
  • ,
  • Gregory Y Lauwers
  • ,
  • Masashi Fukayama

19
2
開始ページ
403
終了ページ
411
記述言語
英語
掲載種別
DOI
10.1007/s10120-015-0493-0

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.

リンク情報
DOI
https://doi.org/10.1007/s10120-015-0493-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25823974
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824805
ID情報
  • DOI : 10.1007/s10120-015-0493-0
  • PubMed ID : 25823974
  • PubMed Central 記事ID : PMC4824805

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