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Different roles for p16 INK 4a ‐ R b pathway and INK 4a/ ARF methylation between adenocarcinomas of gastric cardia and distal stomach
Author(s) -
Xue Liying,
Ouyang Qin,
Li Jie,
Meng Xinxing,
Li Yuehong,
Xing Lingxiao,
Wang Junling,
Yan Xia,
Zhang Xianghong
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12547
Subject(s) - adenocarcinoma , medicine , methylation , immunohistochemistry , cancer research , pathology , gastroenterology , cancer , biology , gene , biochemistry
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 p16 INK 4a ‐retinoblastoma ( R b) pathway and INK 4a/ ARF methylation between gastric cardia and distal adenocarcinomas. Methods Ninety‐six cardia adenocarcinomas and 79 distal samples were analyzed for comparing p16 INK 4a ‐ R b expressions, INK 4a/ ARF deletion, and methylation using immunohistochemistry, polymerase chain reaction, and methylation‐specific polymerase chain reaction. Results The expression of p16 INK 4a 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 p14 ARF compared with distal cases (34.1% vs 57.5%, P < 0.05). The incidence of p16 INK 4a deletion was 20.5% and 15.0%, while p14 ARF deletion was 18.2% and 10.0% in cardia and distal adenocarcinomas, respectively, showing no significant differences between two entities. However, the incidences of p14 ARF and p16 INK 4a methylation in cardia adenocarcinoma were significantly higher than in distal samples (p14 ARF : 61.5% vs 43.6%; p16 INK 4a : 73.1% vs 51.3%, P < 0.05). INK 4a/ ARF methylations were more prevalent in poorly differentiated cardia carcinoma compared with poorly differentiated distal cases. Conclusions There were differences in p16 INK 4a ‐ R b immunotypes and INK 4a/ ARF methylation between two entities, indicating that cardia adenocarcinoma may be different in cell proliferation, differentiation, and gene biomarkers compared with distal gastric adenocarcinoma.