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.
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.
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
Tamotsu
T
Sugai
Mitsunori
M
Tsukahara
Masaki
M
Endoh
Yoshihiro
Y
Shioi
Noriko
N
Takebe
Yoshiharu
Y
Mue
Hiroo
H
Matsushita
Minoru
M
Toyota
Kazuyuki
K
Suzuki
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D019925:Cyclin A / Q000378:metabolism; D005752:Gastric Mucins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018797:Cell Cycle Proteins; D019925:Cyclin A; D005752:Gastric Mucins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen