title: Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach.
abstract: Adenocarcinoma of the gastric cardia (C-Ca) is possibly a specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences in the clinicopathological characteristics between C-Ca and adenocarcinoma of the distal stomach (D-Ca), and also the differences in the expressions of gastric and intestinal phenotypic markers and genetic alterations between the two. The clinicopathological findings in 72 cases with C-Ca were examined and compared with those in 170 cases with D-Ca. The phenotypic marker expressions examined were those of human gastric mucin (HGM), MUC6, MUC2 and CD10. Furthermore, the presence of mutations in the APC, K-ras and p53 genes and the microsatellite instability status of the tumour were also determined. C-Ca was associated with a significantly higher incidence of differentiated-type tumours and lymphatic vessel invasion (LVI) as compared with D-Ca (72.2 vs 48.2%, P=0.0006 and 72.2 vs 55.3%, P=0.0232, respectively). Oesophageal invasion by the tumour beyond the oesophago-gastric junction (OGJ) was found in 56.9% of cases with C-Ca; LVI in the area of oesophageal invasion was demonstrated in 61% of these cases. Also, LVI was found more frequently in cases of C-Ca with oesophageal invasion than in those without oesophageal invasion (82.9 vs 58.1%, P=0.0197). The incidence of undifferentiated-type tumours was significantly higher in cases with advanced-stage C-Ca than in those with early-stage C-Ca (5 vs 36.5%, P=0.0076). A significantly greater frequency of HGM expression in early-stage C-Ca and significantly lower frequency of MUC2 expression in advanced-stage C-Ca was observed as compared with the corresponding values in cases of D-Ca (78.9 vs 52.2%, P=0.0402 and 51.5 vs 84.6%, P=0.0247, respectively). Mutation of the APC gene was found in only one of all cases of C-Ca, and the frequency of mutation of the APC gene was significantly lower in cases of C-Ca than in those of D-Ca (2.4 vs 20.0%, P=0.0108). The observations in this study suggest that C-Ca is a more aggressive tumour than D-Ca. The differences in biological behavior between C-Ca and D-Ca may result from the different histological findings in the wall of the OGJ and the different genetic pathways involved in the carcinogenesis.
authors.affiliation: 1Division of General and Gastroenterological Surgery, Department of Surgery, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. surgery@med.showa-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tajima
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
authors.forename: R
authors.initials: R
authors.lastname: Makino
authors.forename: N
authors.initials: N
authors.lastname: Nishino
authors.forename: Y
authors.initials: Y
authors.lastname: Masuda
authors.forename: S
authors.initials: S
authors.lastname: Aoki
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Morohara
authors.forename: M
authors.initials: M
authors.lastname: Kusano
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002299:Cardia / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D004947:Esophagus / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm