title: Different roles for p16(INK) (4a) -Rb pathway and INK4a/ARF methylation between adenocarcinomas of gastric cardia and distal stomach.
abstract: OBJECTIVE
  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 (Rb) pathway and INK4a/ARF methylation between gastric cardia and distal adenocarcinomas.
  
  
  METHODS
  Ninety-six cardia adenocarcinomas and 79 distal samples were analyzed for comparing p16(INK) (4a) -Rb expressions, INK4a/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). INK4a/ARF methylations were more prevalent in poorly differentiated cardia carcinoma compared with poorly differentiated distal cases.
  
  
  CONCLUSIONS
  There were differences in p16(INK) (4a) -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.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Xue
authors.forename: Qin
authors.initials: Q
authors.lastname: Ouyang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Xinxing
authors.initials: X
authors.lastname: Meng
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Li
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Xing
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Yan
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D013270:Stomach / Q000033:anatomy & histology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein
keywords: INK4a/ARF; distal gastric adenocarcinoma; gastric cardia adenocarcinoma; methylation