Cell kinetics and genetic instabilities in differentiated type early gastric cancers with different mucin phenotype.
To clarify the biological impact and molecular pathogenesis of cellular phenotype in differentiated-type gastric cancers (DGCs), we investigated cell kinetics and genetic instabilities in early stage of DGCs. A total of 43 early gastric cancers (EGCs) were studied. EGCs were divided into 3 phenotypic categories: gastric (G type, n = 11), ordinary (O type, n = 20), and complete intestinal (CI type, n = 12) based on the combination of HGM, ConA, MUC2, and CD10. Proliferative index (PI), apoptotic index (AI), and p53 overexpression were investigated by immunohistochemical staining with anti-Ki-67, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method, and p53 antibody, respectively. Using a high-resolution fluorescent microsatellite analysis system, microsatellite instability (MSI) and loss of heterozygosity (LOH) were examined. Frameshift mutation analysis of transforming growth factor-beta type II receptor (TGF-betaRII) and bcl-2-associated X (BAX) in cancers with MSI was also performed. The mean AI/PI ratio values were 0.04 for G-type, 0.10 for O-type, and 0.13 for CI-type cancers--significantly lower in G type than in O and CI types (P = 0.02 and P = 0.001, respectively). No difference in the incidence of MSI and LOH was seen among the 3 cellular phenotypes. However, the major pattern of MSI, which showed drastic and widely dispersed changes and is related to an increased risk for cancer, was significantly higher in G and O types than in CI type (P <0.005). No frame shift mutations of TGF-betaRII or BAX were found in CI-type cancers. These results indicate that G-type cancers are likely to show more aggressive behaviors than CI-type cancers, and that O-type cancers show the intermediate characteristics of both types. However, the molecular pathogenesis of each phenotypic cancer is not associated with microsatellite alterations.
Shibata
Naomi
N
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Watari
Jiro
J
Fujiya
Mikihiro
M
Tanno
Satoshi
S
Saitoh
Yusuke
Y
Kohgo
Yutaka
Y
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005456:Fluorescent Dyes; D016368:Frameshift Mutation; D005753:Gastric Mucosa / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D007700:Kinetics; D019656:Loss of Heterozygosity / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics*; D009077:Mucins / Q000032:analysis / Q000235:genetics*; D010641:Phenotype; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D019394:Ki-67 Antigen; D009077:Mucins; D016159:Tumor Suppressor Protein p53