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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.

Sugai T, Tsukahara M, Endoh M, Shioi Y, Takebe N, Mue Y, Matsushita H, Toyota M, Suzuki K - BMC Gastroenterol (2010)

Bottom Line: Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10.A Ki-67 positive rate (PR) was also examined.Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Diagnostic Molecular Pathology, Department of Pathology, School of Medicine, Iwate Medical University, 19-1 Morioka City 020-8505, Japan. tsugai@cocoa.ocn.ne.jp

ABSTRACT

Background: Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes.

Methods: Immunostaining for Cyclins D1, A, E, and p21, p27, p53 and beta-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined.

Results: Overexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined.

Conclusions: Our results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.

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A new hypothesis for tumorigenesis of gastric intramucosal differentiated-type cancer as defined by the mucin phenotype.
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Figure 4: A new hypothesis for tumorigenesis of gastric intramucosal differentiated-type cancer as defined by the mucin phenotype.

Mentions: In summary, we propose that the cellular mucin phenotypes of intramucosal differentiated-type adenocarcinomas of the stomach are dependent on distinct cell cycle-related alterations, and that the clinico-pathological findings result from different pathways based on mucin expression: gastric, intestinal and mixed phenotypes. Figure 4 illustrates a novel carcinogenesis model for intramucosal differentiated-type adenocarcinomas that relies on their mucin phenotypes. Based on abnormalities of cell cycle-related proteins, overexpressions of p53 and cyclin A characterize gastric phenotype cancers, whereas overexpression of p27 may be associated with the development of intestinal phenotype cancers. In contrast, mixed-phenotype cancers are characterized by cyclin A overexpression. In addition, mucin phenotypes appear to be characterized by nuclear grade and cell proliferative activity. Three of 190 tumors were of the unclassified type, and this tumor molecular characteristic is not identified. Finally, little is known regarding the distinct molecular alterations that are involved in the pathogenesis of gastric cancer. Further studies will be necessary to address this question.


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 T, Tsukahara M, Endoh M, Shioi Y, Takebe N, Mue Y, Matsushita H, Toyota M, Suzuki K - BMC Gastroenterol (2010)

A new hypothesis for tumorigenesis of gastric intramucosal differentiated-type cancer as defined by the mucin phenotype.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2903504&req=5

Figure 4: A new hypothesis for tumorigenesis of gastric intramucosal differentiated-type cancer as defined by the mucin phenotype.
Mentions: In summary, we propose that the cellular mucin phenotypes of intramucosal differentiated-type adenocarcinomas of the stomach are dependent on distinct cell cycle-related alterations, and that the clinico-pathological findings result from different pathways based on mucin expression: gastric, intestinal and mixed phenotypes. Figure 4 illustrates a novel carcinogenesis model for intramucosal differentiated-type adenocarcinomas that relies on their mucin phenotypes. Based on abnormalities of cell cycle-related proteins, overexpressions of p53 and cyclin A characterize gastric phenotype cancers, whereas overexpression of p27 may be associated with the development of intestinal phenotype cancers. In contrast, mixed-phenotype cancers are characterized by cyclin A overexpression. In addition, mucin phenotypes appear to be characterized by nuclear grade and cell proliferative activity. Three of 190 tumors were of the unclassified type, and this tumor molecular characteristic is not identified. Finally, little is known regarding the distinct molecular alterations that are involved in the pathogenesis of gastric cancer. Further studies will be necessary to address this question.

Bottom Line: Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10.A Ki-67 positive rate (PR) was also examined.Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Diagnostic Molecular Pathology, Department of Pathology, School of Medicine, Iwate Medical University, 19-1 Morioka City 020-8505, Japan. tsugai@cocoa.ocn.ne.jp

ABSTRACT

Background: Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes.

Methods: Immunostaining for Cyclins D1, A, E, and p21, p27, p53 and beta-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined.

Results: Overexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined.

Conclusions: Our results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.

Show MeSH
Related in: MedlinePlus