Differential expression of Pim-3, c-Myc, and p-p27 proteins in adenocarcinomas of the gastric cardia and distal stomach

Tumour Biol. 2014 May;35(5):5029-36. doi: 10.1007/s13277-014-1664-z. Epub 2014 Feb 2.


Gastric cardia adenocarcinoma (GCA) is distinct from adenocarcinoma of the distal stomach because of its different etiological factors, tumor characteristics, and biological behavior. However, its pathogenesis is not fully understood. The purpose of this study is to characterize the role of Pim-3, c-Myc, and p-p27 in the tumorigenesis and progression of different sites of gastric adenocarcinoma by determining its pathogenetic significance. The expression of Pim-3, c-Myc, and p-p27 proteins was evaluated by immunohistochemistry in 140 resection specimens of gastric adenocarcinomas (78 GCAs , 62 DGAs and 20 normal gastric tissues). The level of expression of Pim-3, c-Myc, and p-p27 and the co-expression of all three markers (Pim-3+/c-Myc+/p-p27+) in GCA were significantly lower than that in DGA tumors (P < 0.05). Detailed analysis of the immunoreactivity patterns showed that in DGA, Pim-3 immunoreactivity was associated significantly with poor tumor differentiation, advanced tumor stage, and presence of lymph node metastasis. In addition, c-Myc overexpression correlated with tumor stage and lymph node metastasis, and positive p-p27 expression correlated with poor differentiation and tumor stage. The phenotype of Pim-3(+)/c-Myc(+)/p-p27(+) co-expression was closely correlated with tumor stage and lymph node metastasis (P < 0.05). In contrast, GCA only demonstrated a close correlation of Pim-3 overexpression with poor tumor differentiation and tumor stage (P < 0.05). Our results demonstrate the presence of different expression patterns of Pim-3, c-Myc, p-p27, and Pim-3(+)/c-Myc(+)/p-p27(+) and their clinicopathologic significance in GCA and DGA tumors. Our results add support to the notion that distinct molecular mechanisms may be involved in the development and progression of adenocarcinomas from the gastric cardia and distal portion of stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / etiology
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Cardia*
  • Cyclin-Dependent Kinase Inhibitor p27 / analysis*
  • Cyclin-Dependent Kinase Inhibitor p27 / physiology
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Protein Serine-Threonine Kinases / analysis*
  • Protein Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-myc / analysis*
  • Proto-Oncogene Proteins c-myc / physiology
  • Stomach Neoplasms / chemistry
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / pathology*


  • CDKN1B protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Cyclin-Dependent Kinase Inhibitor p27
  • PIM3 protein, human
  • Protein Serine-Threonine Kinases