Genetic differences stratified by PCR-based microsatellite analysis in gastric intramucosal neoplasia

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2017-03, Vol.20 (2), p.286-296
• Main Authors: Sugai, Tamotsu, Sugimoto, Ryo, Habano, Wataru, Endoh, Masaki, Eizuka, Makoto, Tsuchida, Koudai, Yamamoto, Eiichiro, Kawasaki, Keisuke, Yanai, Syunichi, Matsumoto, Takayuki, Suzuki, Hiromu
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Research; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; DNA Methylation; Endoscopic Mucosal Resection; Female; Follow-Up Studies; Gastric cancer; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastroenterology; Humans; Immunoenzyme Techniques; Male; Medicine; Medicine & Public Health; Microsatellite Instability; Middle Aged; Neoplasm Staging; Oncology; Original Article; Polymerase Chain Reaction; Prognosis; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Surgical Oncology
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-016-0616-2

Background Although genetic alterations in patients with advanced gastric cancer have been extensively studied, those in patients with intramucosal neoplasia (IMN) are still poorly understood. Methods We evaluated genetic differences in 158 IMNs, including 51 low-grade dysplasias, 58 high-grade dysplasias (HGDs), 30 intramucosal cancers (IMCs), and 19 mixed tumors (composed of IMC and HGD within the same tumor), using PCR-based microsatellite analysis [allelic imbalance (AI) and microsatellite instability (MSI)]. We classified the DNA methylation status as a hypermethylated epigenome, a moderately methylated epigenome, or a hypomethylated epigenome. In addition, p53 overexpression, β-catenin nuclear localization, and mucin expression were also examined. Results From cluster analysis, the IMNs examined were categorized into four subgroups as follows. Tumors in subgroup 1 were characterized by MSI-high status, a hypermethylated epigenome, and loss or reduction of expression of MLH-1. Tumors in subgroup 2 showed a mixed pattern consisting of AI and MSI. In contrast, tumors in subgroup 3, which showed accumulation of multiple AIs, were closely associated with HGD, IMC, or mixed tumor and exhibited nuclear expression of β-catenin. Tumors in subgroup 4, which were generally low-grade dysplasias, exhibited a low frequency of AIs and no MSI. Although the mucin phenotype was not correlated with any subgroup, expression of mucin was associated with some subgroups. Overexpression of p53 was common in all subgroups. Conclusion The approach described herein was useful for studying genetic differences in IMNs. In addition, we suggest that stratification of genetic differences may help to identify genetic molecular profiles in IMNs.