title: Molecular and cellular phenotypic profiles of gastric noninvasive neoplasia.
abstract: According to the Padova international classification, 52 gastric noninvasive neoplasias (NIN) were classified as follows: 20 low-grade NIN (L-NIN); 9 high-grade NIN including suspicion for carcinoma without invasion (H-NIN); and 23 high-grade NIN including carcinoma without invasion (Ca-NIN). The molecular and cellular phenotypic profiles were investigated and compared. The APC gene was mutated in seven (35%) L-NIN, two (22%) H-NIN, and two (9%) Ca-NIN tumors; APC mutations were significantly more frequent in L-NIN compared with Ca-NIN tumors (p < 0.05). Mutations of the p53 gene were found in five (22%) Ca-NIN tumors but were not observed in L-NIN or H-NIN tumors (p < 0.05). Loss of heterozygosity involving at least one chromosomal locus was detected in 14 (61%) Ca-NIN tumors but was not detected in L-NIN or H-NIN tumors. High-frequency microsatellite instability (MSI-H) was detected in one (5%) L-NIN tumor and in six (26%) Ca-NIN tumors. The frequencies of loss of heterozygosity and MSI-H were significantly higher in Ca-NIN than in L-NIN or H-NIN tumors (p < 0.05). Nuclear accumulation of p53 protein was detected in no L-NIN tumors, 1 (11%) H-NIN tumor, and 10 (44%) Ca-NIN tumors (p < 0.01). All tumors with loss of hMLH1 expression exhibited MSI-H (p < 0.01). Cellular phenotypic analysis revealed that seven (35%) L-NIN tumors and one (4%) Ca-NIN tumor had complete-type intestinal metaplastic phenotype and that one (5%) L-NIN tumor and one (4%) Ca-NIN tumor had a gastric foveolar epithelial phenotype, whereas the remaining tumors exhibited an ordinary phenotype. Thus, the complete-type intestinal metaplastic phenotype was more characteristic of L-NIN tumors than of H-NIN or Ca-NIN tumors (p < 0.01). In summary, the Padova international classification correlated with both the molecular and cellular phenotypic profiles. In practice, p53 and hMLH1 immunohistochemistry discriminated Ca-NIN from L-NIN and H-NIN tumors.
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.forename: Teiichiro
authors.initials: T
authors.lastname: Honda
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D002352:Carrier Proteins; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D000070957:MutL Protein Homolog 1