Journal of Cancer Research and Clinical Oncology

, Volume 134, Issue 4, pp 481–488

Aberrant Pim-3 expression is involved in gastric adenoma–adenocarcinoma sequence and cancer progression

  • Hua-Chuan Zheng
  • Koichi Tsuneyama
  • Hiroyuki Takahashi
  • Shigeharu Miwa
  • Toshiro Sugiyama
  • Boryana Konstantinova Popivanova
  • Chifumi Fujii
  • Kazuhiro Nomoto
  • Naofumi Mukaida
  • Yasuo Takano
Original Paper

DOI: 10.1007/s00432-007-0310-1

Cite this article as:
Zheng, HC., Tsuneyama, K., Takahashi, H. et al. J Cancer Res Clin Oncol (2008) 134: 481. doi:10.1007/s00432-007-0310-1

Abstract

Purpose

Pim-3, a member of the proto-oncogene Pim family with serine/threonine kinase activity was aberrantly expressed in cancerous lesions of endoderm-derived organs such as liver, pancreas, and colon. The aim of this study was to clarify the role of Pim-3 expression in the tumorigenesis and the development of gastric carcinomas.

Methods

Pim-3 expression was immunohistochemically examined on the tissue microarrays containing primary (n = 285) and metastastic (n = 37) sites of gastric carcinomas, in comparison with adenoma (n = 48) and non-cancerous mucosa (n = 84). It was also compared with the clinicopathological parameters of gastric carcinomas.

Results

Pim-3 expression was enhanced in adenoma (64.6%) and metastasis sites of gastric carcinoma (73.0%), to a lesser degree in primary sites of gastric carcinoma (39.3%) when compared to non-cancerous mucosa (13.1%, < 0.0001). Pim-3 expression levels were higher in intestinal-type than diffuse-type gastric carcinoma (p = 0.018). Pim-3 expression was closely correlated with sex (p = 0.047), lymphatic (p = 0.019) and venous invasion (p = 0.014). Pim-3 expression was correlated significantly with vascular endothelial growth factor (VEGF, = 0.009) and extracellular matrix metalloproteinase inducer (EMMPRIN, = 0.032), both of which are presumed to be involved in neovascularization, a crucial step for metastasis. On the contrary, phosphatase and tensin homology deleted from human chromosome 10 (Pten) negative gastric carcinomas exhibited higher Pim-3 expression than Pten positive ones (= 0.042). There was no relationship between Pim-3 expression and MVD in gastric carcinomas (= 0.715). Furthermore, patients with Pim-3 positive gastric cancer, showed a lower cumulative survival rate than those with Pim-3 negative gastric cancer (= 0.014) and Pim-3 positive was also identified as an independent prognostic factor for gastric carcinoma patients (= 0.006).

Conclusions

Aberrant Pim-3 expression was involved in gastric adenoma–adenocarcinoma sequence and subsequent invasion and metastasis process in gastric cancer. Moreover, Pim-3 may be employed to predict the prognosis of gastric cancer patients. Distinct Pim-3 expression underlies the molecular mechanisms for the differentiation of intestinal-type and diffuse-type carcinomas.

Keywords

Angiogenesis Gastric carcinoma Invasion Metastasis Pim-3 Prognosis 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Hua-Chuan Zheng
    • 1
    • 5
  • Koichi Tsuneyama
    • 1
    • 2
  • Hiroyuki Takahashi
    • 1
  • Shigeharu Miwa
    • 3
  • Toshiro Sugiyama
    • 3
  • Boryana Konstantinova Popivanova
    • 4
  • Chifumi Fujii
    • 4
  • Kazuhiro Nomoto
    • 1
  • Naofumi Mukaida
    • 4
  • Yasuo Takano
    • 1
  1. 1.Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  2. 2.21st Century COE Program, Graduate School of Medical and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  3. 3.Department of Gastroenterology and Hematology, Graduate School of Medical and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  4. 4.Division of Molecular Bioregulation, Cancer Research InstituteKanazawa UniversityKanazawaJapan
  5. 5.College of Basic MedicineChina Medical UniversityShenyangChina

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