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 ¼ 0.0006 and 72.2 vs 55.3%, P ¼ 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 ¼ 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 ¼ 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 ¼ 0.0402 and 51.5 vs 84.6%, P ¼ 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 ¼ 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.

Meta-analysis demonstrates that the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene 609 C>T polymorphism is associated with increased gastric cancer risk in Asians

“…For example, CAC are strongly correlated with chronic gastroesophageal reflux (Wijnhoven et al, 1999) and with cigarette smoking (Gammon et al, 1997), and have a higher rate of lymph node metastasis and unfavorable prognosis (El-Rifai et al, 2001;Tajima et al, 2007), while Hp infection has been proven to be more relevant to GAC development (Xue et al, 2011). In the subgroup analyses by type of gastric cancer, we found significantly increased risk with all genetic models in GAC subgroup; however, nearly no remarkable changes in risk estimates was observed in CAC and GSCC subgroups for the NQO1 gene C609T polymorphisms.…”

Differences of immunophenotypic markers and signaling molecules between adenocarcinomas of gastric cardia and distal stomach

“…Accordingly, it might be a special subtype or an independent entity of gastric carcinoma. Maeda et al [8] reported that the cardiac carcinoma had a higher rate of lymph node metastasis and unfavorable prognosis than did noncardiac tumors [9,10]. Meanwhile, Helicobacter pylori (Hp) infection was proven to be a key factor in adenocarcinomas of distal stomach, whereas the role of Hp in cardiac tumors was controversial [11,12].…”

Loss of heterozygosity at chromosomes 1p35-pter, 4q, and 18q and protein expression differences between adenocarcinomas of the distal stomach and gastric cardia

“…In the past several years, the incidence of AGC exhibited an increasing trend in the high-incidence areas of gastric adenocarcinoma in China [4,5]. Recent studies indicate that AGC and adenocarcinoma of the distal stomach (ADS) differ in their clinicopathologic and epidemiological characteristics [6,7]. However, the etiology of AGC and its relation to ADS remain unsettled.…”