Clinicopathological and molecular alterations in early gastric cancers with the microsatellite instability‐high phenotype. Issue 7 (17th December 2015)

• Record Type: Journal Article
• Authors: Sugimoto, Ryo; Sugai, Tamotsu; Habano, Wataru; Endoh, Masaki; Eizuka, Makoto; Yamamoto, Eiichiro; Uesugi, Noriyuki; Ishida, Kazuyuki; Kawasaki, Tomonori; Matsumoto, Takayuki; Suzuki, Hiromu
• Is Part Of: International journal of cancer. Volume 138:Issue 7(2016:Apr. 01)
• Page Start: 1689
• Page End: 1697
• Publication Date: 2015-12-17
• Subjects: allelic imbalance -- early gastric cancer -- microsatellite instability -- methylation -- papillary adenocarcinoma; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29916
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : The relevance of the clinicopathological and molecular features of early gastric cancers (EGCs) having the microsatellite instability (MSI)‐high phenotype has not been clearly defined in sporadic gastric carcinogenesis. Here, we examined the clinicopathological and molecular characteristics of EGC according to MSI status in 330 patients with EGC (intestinal‐type adenocarcinoma). Tumors were classified as MSI‐high (45 cases), MSI‐low (9 cases), or microsatellite stable (MSS; 276 cases). The specimens were examined using a combination of polymerase chain reaction (PCR)‐microsatellite assays and PCR‐pyrosequencing to detect chromosomal allelic imbalances in multiple cancer‐related chromosomal loci, MSI, gene mutations ( KRAS and BRAF ) and methylation status [high methylation epigenome (HME), intermediate methylation epigenome and low methylation epigenome]. In addition, the expression levels of various target proteins were examined using immunohistochemistry. Interestingly, EGC with the MSI phenotype showed distinct papillary features. The expression of gastric mucin was more frequent in EGC with the MSI phenotype, while p53 overexpression was common in EGCs, irrespective of MSI status. The frequency of HME was significantly higher in EGCs with the MSI phenotype than in EGCs with the MSS phenotype. Although there was a low frequency of allelic imbalance in EGCs with the MSI phenotype, some markers of allelic imbalance were more frequently detected in EGCs with the MSI‐high phenotype than in EGCs with the MSS phenotype. KRAS and BRAF mutations were rare in EGCs. Thus, the MSI phenotype in EGC is a major precursor lesion in gastric cancer and is characterized by distinct clinicopathological and molecular features. Abstract : What's new? The relevance of the clinicopathological and molecular features of early gastric cancers with the microsatellite instability (MSI)‐high phenotype remains to be clarified in sporadic gastric carcinogenesis. This study shows that early gastric cancers with the MSI‐high phenotype exhibit distinct histological features and accumulation of both genomic damage and MSI within the same tumors. In regions with genomic damage, the frequencies of 3p and 22q AI were significantly higher in the MSI‐high phenotype than in the microsatellite stable phenotype. The treatment strategies for patients with gastric cancers having the MSI‐high phenotype may thus need to differ from patients with colorectal cancer.