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

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%, p < 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, p = 0.009) and extracellular matrix metalloproteinase inducer (EMMPRIN, p = 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 (p = 0.042). There was no relationship between Pim-3 expression and MVD in gastric carcinomas (p = 0.715). Furthermore, patients with Pim-3 positive gastric cancer, showed a lower cumulative survival rate than those with Pim-3 negative gastric cancer (p = 0.014) and Pim-3 positive was also identified as an independent prognostic factor for gastric carcinoma patients (p = 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.

• Authors: Hua-Chuan Zheng, Koichi Tsuneyama, Hiroyuki Takahashi, Shigeharu Miwa, Toshiro Sugiyama, Boryana Konstantinova Popivanova, Chifumi Fujii, Kazuhiro Nomoto, Naofumi Mukaida, Yasuo Takano
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 134 Issue 4 Pg. 481-8 (Apr 2008) ISSN: 0171-5216 [Print] Germany
• PMID: 17876606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD34
• MAS1 protein, human
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• Vascular Endothelial Growth Factor A
• PIM3 protein, human
• Protein Serine-Threonine Kinases

Topics

• Adenocarcinoma (blood supply, chemistry, mortality, pathology)
• Adenoma (blood supply, chemistry, mortality, pathology)
• Adult
• Aged
• Antigens, CD34 (analysis)
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Protein Serine-Threonine Kinases (analysis)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins (analysis)
• Stomach Neoplasms (blood supply, chemistry, mortality, pathology)
• Tissue Array Analysis
• Vascular Endothelial Growth Factor A (analysis)