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Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes

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Kim Joo-Yeun, ½Å³ª¸®, ±è¾Æ·Õ, ÀÌÇöÁ¤, ¹Ú¿ø¿µ, ±èÁö¿¬, ÀÌâÈÆ, Çã±â¿µ, ¹ÚµµÀ±,
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 ( Kim Joo-Yeun ) 
Pusan National University Hospital Department of Pathology

½Å³ª¸® ( Shin Na-Ri ) 
Pusan National University Hospital Department of Pathology
±è¾Æ·Õ ( Kim Ah-Rong ) 
Pusan National University Hospital Department of Pathology
ÀÌÇöÁ¤ ( Lee Hyun-Jeong ) 
Pusan National University Hospital Department of Pathology
¹Ú¿ø¿µ ( Park Won-Young ) 
Pusan National University Hospital Department of Pathology
±èÁö¿¬ ( Kim Jee-Yeon ) 
Pusan National University Hospital Department of Pathology
ÀÌâÈÆ ( Lee Chang-Hun ) 
Pusan National University Hospital Department of Pathology
Çã±â¿µ ( Huh Gi-Yeong ) 
Pusan National University Hospital Department of Forensic Medicine
¹ÚµµÀ± ( Park Do-Youn ) 
Pusan National University Hospital Department of Pathology

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 (¡Ã2/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 (¡Ã10% of mass, p=0.031), tumorinfiltrating 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.

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Stomach; Adenocarcinoma; Microsatellite instability; Mucin; Survival

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