Different roles for p16INK4a-Rb pathway and INK4a/ARF methylation between adenocarcinomas of gastric cardia and distal stomach

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Background and Aim:

The incidence of distal gastric adenocarcinoma has significantly decreased, but gastric cardia adenocarcinoma has been on the rise. Cardia adenocarcinoma might be a specific entity distinct from the carcinoma of the rest stomach. The aim was to explore putative differences in p16INK4a-retinoblastoma (Rb) pathway and INK4a/ARF methylation between gastric cardia and distal adenocarcinomas.


Ninety-six cardia adenocarcinomas and 79 distal samples were analyzed for comparing p16INK4a-Rb expressions, INK4a/ARF deletion, and methylation using immunohistochemistry, polymerase chain reaction, and methylation-specific polymerase chain reaction.


The expression of p16INK4a in cardia adenocarcinoma (43.2%) was significantly lower than in distal cases (75.0%, P < 0.05). As well, cardia adenocarcinoma showed lower expression of p14ARF compared with distal cases (34.1% vs 57.5%, P < 0.05). The incidence of p16INK4a deletion was 20.5% and 15.0%, while p14ARF deletion was 18.2% and 10.0% in cardia and distal adenocarcinomas, respectively, showing no significant differences between two entities. However, the incidences of p14ARF and p16INK4a methylation in cardia adenocarcinoma were significantly higher than in distal samples (p14ARF: 61.5% vs 43.6%; p16INK4a: 73.1% vs 51.3%, P < 0.05). INK4a/ARF methylations were more prevalent in poorly differentiated cardia carcinoma compared with poorly differentiated distal cases.


There were differences in p16INK4a-Rb immunotypes and INK4a/ARF methylation between two entities, indicating that cardia adenocarcinoma may be different in cell proliferation, differentiation, and gene biomarkers compared with distal gastric adenocarcinoma.

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