Low-grade gastric adenomas/dysplasias: phenotypic expression, DNA ploidy pattern, and LOH at microsatellites linked to the APC gene.
The adenoma-adenocarcinoma sequence in the colon is generally accepted. Regarding the stomach, however, opinions about tumorigenesis are different. We analyzed the phenotypes, DNA ploidy patterns, and microsatellite regions linked to adenomatous polyposis coli (APC) gene on chromosome 5q of low-grade gastric adenomas/dysplasias, Vienna Category 3, to investigate whether these lesions have the potential to become adenocarcinomas. Phenotypes were determined by immunohistochemical staining with monoclonal antibodies MUC2, MUC5AC, MUC6, CD10, and Cdx2. DNA ploidy patterns were determined by static cytofluorometry. Microsatellite analyses were performed using Genescan on genetic analyzer ABI PRISM 310. None of the 15 cases showed coexisting high-grade adenomas/dysplasias or adenocarcinoma. Eighty percent of the cases had the complete intestinal phenotype, and the remainder showed slight MUC6 positivity for the intestinal phenotype. All cases were positive for Cdx2 and showed diploid DNA. In addition, 46.7% of the cases exhibited loss of heterozygosity (LOH) of chromosome 5q. Except for one case, 5q-LOH was detected at a single locus in cases with the complete intestinal phenotype. According to previous studies, most gastric adenocarcinomas have the gastric phenotype and no 5q-LOH. These results suggest that low-grade gastric adenomas/dysplasias, Vienna category 3, seldom progress to gastric adenocarcinomas of the differentiated type.
Tanaka
Aiko
A
Department of Pathology, Shiga University of Medical Science, Otsu, Japan; Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
Takemura-Tsukashita
Shizuki
S
Kushima
Ryoji
R
Sugihara
Hiroyuki
H
Fujiyama
Yoshihide
Y
Hattori
Takanori
T
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002895:Chromosomes, Human, Pair 5; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D005838:Genotype; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008856:Microscopy, Fluorescence; D055271:Mucin 5AC; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins / Q000032:analysis; D009367:Neoplasm Staging; D015260:Neprilysin / Q000032:analysis; D010641:Phenotype; D011003:Ploidies; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins; D015260:Neprilysin