title: Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations.
abstract: OBJECTIVE
  To clarify the relations between tumor differentiation phenotype and tumor invasion or genetic alterations in gastric differentiated-type tumors.
  
  
  METHODS
  We examined the tumor differentiation phenotype, the presence of mutations in APC and p53, and the microsatellite instability (MSI) status in 48 gastric adenomas and 171 differentiated-type carcinomas. The tumor differentiation phenotype was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10. The tumors were then classified into gastric- (G-), gastric and intestinal mixed- (GI-), or intestinal- (I-) phenotypes, according to the immunopositivity of the above markers. The presence of mutations in APC and p53 and the MSI status were also investigated in all the tumors.
  
  
  RESULTS
  Gastric adenomas were significantly associated with CD10 expression, I-phenotype tumors and the presence of APC mutations, compared with carcinomas (66.7% vs 25.1%, P < 0.0001; 56.3% vs 14.6%, P < 0.0001; 39.6% vs 14.0%, P < 0.0001, respectively) and inversely associated with expressions of HGM and MUC6 and the presence of p53 mutations (10.4% vs 62.6%, P < 0.0001; 39.6% vs 64.3%, P = 0.003; 2.0% vs 26.3%, P = 0.001, respectively). The frequency of APC mutations was significantly higher in HGM-negative tumors, MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors than in HGM-positive tumors, MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors (32.7% vs 7.1%, P < 0.0001; 27.8% vs 14.0%, P = 0.0182; 37.3% vs 10.4%, P < 0.0001; and 38.5% vs 9.5%, P = 0.0017, respectively). The frequency of MSI was significantly higher in MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors than in MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors (24.8% vs 6.7%, P = 0.0009; 22.2% vs 8.0%, P = 0.0143; and 28.6% vs 9.6%, P = 0.0353, respectively).
  
  
  CONCLUSIONS
  The tumor differentiation phenotype is closely related to tumor invasion and genetic alterations in gastric differentiated-type tumors.
authors.affiliation: Department of Surgery, Division of General and Gastroenterological Surgery, Showa University, School of Medicine, Tokyo, Japan.
authors.forename: Kimiyasu
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tajima
authors.forename: Reiko
authors.initials: R
authors.lastname: Makino
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Nishino
authors.forename: Shigeo
authors.initials: S
authors.lastname: Aoki
authors.forename: Masanori
authors.initials: M
authors.lastname: Kato
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Morohara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kaetsu
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kusano
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D000236:Adenoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005752:Gastric Mucins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D017491:Genes, APC / Q000502:physiology; D052138:Genes, Neoplasm / Q000235:genetics* / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000235:genetics*; D015260:Neprilysin / Q000032:analysis / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm; D005752:Gastric Mucins; C524625:MUC2 protein, human; C524734:MUC6 protein, human; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins; D015260:Neprilysin