Document Detail

Three independent genetic profiles based on mucin expression in early differentiated-type gastric cancers--a new concept of genetic carcinogenesis of early differentiated-type adenocarcinomas.
MedLine Citation:
PMID:  15154009     Owner:  NLM     Status:  MEDLINE    
Recent molecular studies have shown that the genetic profiles of differentiated-type adenocarcinomas of the stomach are associated with distinct cellular mucin phenotypes (gastric- intestinal- and mixed-phenotypes). Therefore, we examined whether these cellular mucin phenotypes reflect specific molecular genetic alterations, and whether the phenotypes can be used to help categorize the intramucosal neoplasias of gastric tumors. We subclassified tumors into four cellular phenotypes using immunohistochemical mucin analysis. In all, 62 early gastric carcinomas (gastric-phenotype, 13; intestinal-phenotype, 17; mixed-phenotype, 31; unclassified-phenotype, 1) were examined using a combination of polymerase chain reaction microsatellite assays and immunohistochemical analysis in order to detect chromosomal allelic losses of multiple cancer-related chromosomal loci (1p, 3p. 4p, 5q, 8p, 9p, 13p, 17p, 18q and 22q), microsatellite instability (MSI), and overexpression of the p53 protein. In addition, we analyzed the relationship between MSI status and hMLH1 promoter hypermethylation, which is thought to be a cause of high MSI status. For gastric phenotype cancers, the frequency of 3p allelic loss was higher than that of other microsatellite markers, whereas 5q allelic loss was frequently found in intestinal phenotype cancers. The genetic profile of mixed phenotype cancers is comprised of two distinct genetic types: LOH and MSI types. In the former, 5q, 3p and 18q allelic losses are seen frequently in intramucosal carcinomas. On the other hand, 17p, 1p and 9p allelic losses are associated with the development of submucosal carcinomas. MSI was observed only in mixed phenotype cancers (six of 31 mixed phenotype cancers). Overexpression of the p53 protein is common in differentiated-type gastric cancers. In addition, the MSI status of the tumor cells was correlated with the extent of hypermethylation of the hMLH1 promoter. We suggest that the cellular mucin phenotypes of the differentiated-type adenocarcinomas result from distinct genetic alterations.
Tamotsu Sugai; Wataru Habano; Noriyuki Uesugi; Yu-Fei Jao; Shin-ichi Nakamura; Kaoru Abe; Akinori Takagane; Masanori Terashima
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc     Volume:  17     ISSN:  0893-3952     ISO Abbreviation:  Mod. Pathol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-16     Completed Date:  2005-01-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8806605     Medline TA:  Mod Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1223-34     Citation Subset:  IM    
Division of Pathology, Central Clinical Laboratory, Iwate Medical University, Morioka, Japan.
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MeSH Terms
Adaptor Proteins, Signal Transducing
Adenocarcinoma / genetics,  metabolism,  pathology*
Aged, 80 and over
Carrier Proteins
DNA Methylation
DNA, Neoplasm / genetics,  metabolism
Intestinal Neoplasms / genetics,  metabolism,  pathology
Loss of Heterozygosity*
Microsatellite Repeats
Middle Aged
Mucin 5AC
Mucins / analysis,  biosynthesis*
Neoplasm Proteins / genetics
Nuclear Proteins
Polymerase Chain Reaction
Promoter Regions, Genetic / genetics
Stomach Neoplasms / genetics,  metabolism,  pathology*
Tumor Suppressor Protein p53 / analysis
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Carrier Proteins; 0/DNA, Neoplasm; 0/MLH1 protein, human; 0/MUC2 protein, human; 0/MUC5AC protein, human; 0/Mucin 5AC; 0/Mucin-2; 0/Mucins; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/Tumor Suppressor Protein p53

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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