Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

Sugai, Tamotsu; Tsukahara, Mitsunori; Endoh, Masaki; Shioi, Yoshihiro; Takebe, Noriko; Mue, Yoshiharu; Matsushita, Hirokazu; Toyota, Minoru; Suzuki, Kazuyuki

doi:10.1186/1471-230x-10-55

Cited by 19 publications

(37 citation statements)

References 34 publications

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“…Previous studies have shown that mucin expression in tumor cells plays a major role in gastric carcinogenesis [16,17]. In the present study, whereas the MSI-high phenotype (subgroup 1) was categorized by the expression of either mucin 5AC or mucin 6, phenotypic expression in subgroup 3 or subgroup 4 was closely associated with CD10 expression.…”

Section: Discussionmentioning

confidence: 46%

“…intestinal-type adenocarcinoma is thought to be distinct from diffuse-type adenocarcinoma with respect to gastric carcinogenesis [16,24]. In the present study, intestinal-type IMNs, including differentiated-type GC, were the main target lesions used to identify molecular characteristics of early gastric carcinogenesis.…”

Section: Discussionmentioning

confidence: 75%

“…Intestinal-type GCs are often observed in the context of Helicobacter pylori-associated chronic gastritis, atrophy, and intestinal metaplasia, which may be precursors of the dysplastic changes that evolve into this type of carcinoma (or paracancerous lesion) [16]. Diffuse-type GCs are also associated with H. pylori infection, but arise independently of intestinal metaplasia [24].…”

Section: Discussionmentioning

confidence: 99%

“…Immediately after excision, specimens were fixed in 20 % neutral buffered formalin, embedded in paraffin wax, cut into 4-lm-thick paraffin sections, and stained with hematoxylin and eosin for routine light microscopy [16]. For immunohistochemical staining, additional serial 3-lmthick sections were cut from paraffin-embedded tissues and placed on poly(L-lysine)-coated glass slides.…”

Section: Immunohistochemistrymentioning

confidence: 99%

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

et al. 2016

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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, b-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 b-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.

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Section: Discussionmentioning

confidence: 46%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

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

et al. 2016

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“…Cyclin D1 and E Increased cyclin T1 expression as a favorable prognostic factor in treating gastric adenocarcinoma are the key regulators of progression through the G1 phase of the cell cycle (13,14). Overexpression of cyclin D1 and E is considered an early biomarkers of gastric cancer (15).…”

Section: Introductionmentioning

confidence: 99%

Increased cyclin T1 expression as a favorable prognostic factor in treating gastric adenocarcinoma

Jin¹,

Lin²,

Chen³

et al. 2015

Oncology Letters

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Abstract. The expression of cyclin A, B1, D1 and E in gastric adenocarcinoma is known to be associated with clinical outcome. However, few studies have investigated the role of cyclin T1 and cyclin-dependent kinase 9 (CDK9) in gastric adenocarcinoma. Therefore, this study assessed the clinical significance of cyclin T1 and CDK9 expression in gastric adenocarcinoma. A total of 39 gastric adenocarcinoma patients received either radical total or distal gastrectomy in this study. Surgical tissue slides were stained with CDK9 and cyclin T1 antibodies, and immunohistochemistry scores and disease-free survival (DFS) rates were analyzed. Among the 19 patients with tumor-recurrent or distant metastasis, 16 were recorded as exhibiting low expression of cyclin T1. The remaining three patients exhibited high expression of the antibody. The results of patients with a higher T stage, N stage and tumor grade were less favorable. For patients with adenocarcinoma, the percentage of tissue slides stained with cyclin T1 was significantly higher than for those with normal stomach epithelia. The DFS rates of patients with low expression of cyclin T1 were significantly associated with poorer DFS rates. In conclusion, high expression of cyclin T1 is a favorable prognostic factor in treating patients with stomach adenocarcinoma.

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Molecular profiling and comprehensive genome-wide analysis of somatic copy number alterations in gastric intramucosal neoplasias based on microsatellite status

et al. 2018

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BackgroundWe attempted to identify the molecular profiles of gastric intramucosal neoplasia (IMN; low-grade dysplasia, LGD; high-grade dysplasia, HGD; intramucosal cancer, IMC) by assessing somatic copy number alterations (SCNAs) stratified by microsatellite status (microsatellite stable, MSS; microsatellite instable, MSI). Thus, microsatellite status was determined in 84 tumors with MSS status and 16 tumors with MSI status.MethodsOne hundred differentiated type IMNs were examined using SCNAs. In addition, genetic mutations (KRAS, BRAF, PIK3CA, and TP53) and DNA methylation status (low, intermediate and high) were also analyzed. Finally, we attempted to identify molecular profiles using a hierarchical clustering analysis.ResultsThree patterns could be categorized according to SCNAs in IMNs with the MSS phenotype: subgroups 1 and 2 showing a high frequency of SCNAs, and subgroup 3 displaying a low frequency of SCNAs (subgroup 1 > 2 > 3 for SCNA). Subgroup 1 could be distinguished from subgroup 2 by the numbers of total SCNAs (gains and losses) and SCN gains (subgroup 1 > 2). The SCNA pattern of LGD was different from that of HGD and IMC. Moreover, IMNs with the MSI phenotype could be categorized into two subtypes: high frequency of SCNAs and low frequency of SCNAs. Genetic mutations and DNA methylation status did not differ among subgroups in IMNs.ConclusionMolecular profiles stratified by SCNAs based on microsatellite status may be useful for elucidation of the mechanisms of early gastric carcinogenesis.Electronic supplementary materialThe online version of this article (10.1007/s10120-018-0810-5) contains supplementary material, which is available to authorized users.

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Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

Cited by 19 publications

References 34 publications

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

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

Increased cyclin T1 expression as a favorable prognostic factor in treating gastric adenocarcinoma

Molecular profiling and comprehensive genome-wide analysis of somatic copy number alterations in gastric intramucosal neoplasias based on microsatellite status

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