title: Microsatellite instability status in gastric cancer: a reappraisal of its clinical significance and relationship with mucin phenotypes.
abstract: BACKGROUND
  Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear.
  
  
  METHODS
  MSI status was assessed in 414 cases of gastric cancer using polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed.
  
  
  RESULTS
  Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (≥2/high power field, p<0.001), expanding growth patterns (p=0.038), gastric predominant mucin phenotypes (p=0.028), and MUC6 expression (p=0.016). Tumor necrosis (≥10% of mass, p=0.031), tumor-infiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p=0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197).
  
  
  CONCLUSIONS
  Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.
authors.affiliation: Department of Pathology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.
authors.forename: Joo-Yeun
authors.initials: JY
authors.lastname: Kim
authors.forename: Na Ri
authors.initials: NR
authors.lastname: Shin
authors.forename: Ahrong
authors.initials: A
authors.lastname: Kim
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Park
authors.forename: Jee-Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Chang-Hun
authors.initials: CH
authors.lastname: Lee
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Huh
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Park
keywords: Adenocarcinoma; Microsatellite instability; Mucin; Stomach; Survival