Nuclear expression of N-myc downstream regulated gene 1/Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer

Kawahara,Akihiko; Akiba,Jun; Hattori,Satoshi; Yamaguchi,Tomohiko; Abe,Hideyuki; Taira,Tomoki; Ureshino,Hiroki; Murakami,Yuichi; Watari,Kosuke; Koufuji,Kikuo; Shirouzu,Kazuo; Kuwano,Michihiko; Ono,Mayumi; Kage,Masayoshi

doi:10.3892/etm.2011.222

Nuclear expression of N-myc downstream regulated gene 1/Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer

Authors:
- Akihiko Kawahara
- Jun Akiba
- Satoshi Hattori
- Tomohiko Yamaguchi
- Hideyuki Abe
- Tomoki Taira
- Hiroki Ureshino
- Yuichi Murakami
- Kosuke Watari
- Kikuo Koufuji
- Kazuo Shirouzu
- Michihiko Kuwano
- Mayumi Ono
- Masayoshi Kage
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Affiliations: Department of Diagnostic Pathology, Kurume University Hospital, Kurume 830-0011, Japan, Department of Pathology, Kurume University School of Medicine, Kurume, Japan, Biostatistics Center, Kurume University, Kurume, Japan, Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, Department of Surgery, Kurume University School of Medicine, Kurume, Japan, Laboratory of Molecular Cancer Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
Published online on: March 2, 2011 https://doi.org/10.3892/etm.2011.222
Pages: 471-479

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Abstract

Expression of N-myc downstream regulated gene 1 (NDRG1)/Ca2+-associated protein 43 (Cap43) in cancer cells is a predictive marker of good or poor prognosis depending on tumor type. In this study, we examined whether NDRG1/Cap43 is a marker of good or poor prognosis in gastric cancer patients, and whether it is associated with tumor stromal responses, including angiogenesis and macrophage infiltration. The expression levels of NDRG1/Cap43, the number of CD68-positive macrophages and the CD34-positive microvessel density were analyzed by immunohistochemistry in 129 gastric cancer patients, including 65 with the intestinal type and 64 with the diffuse type. The expression of NDRG1/Cap43 in the nucleus and the membrane was evaluated. Nuclear NDRG1/Cap43 expression was found in 20/65 (30.8%) patients with the intestinal type and in 9/64 (14.1%) patients with the diffuse type of gastric cancer. Nuclear NDRG1/Cap43 expression was significantly associated with pathological stage in the intestinal type (P=0.002), but not in the diffuse type (P=0.039). Nuclear NDRG1/Cap43 expression was also closely associated with infiltrating macrophages (P=0.001) and tumor angiogenesis (P=0.001) in the intestinal type. Furthermore, nuclear NDRG1/Cap43 expression was associated with poor prognosis in both the intestinal (P=0.001) and the diffuse types of gastric cancer (P=0.047). By contrast, membranous NDRG1/Cap43 expression was not associated with the overall survival of gastric cancer patients with either the intestinal or diffuse type of gastric cancer. The expression of NDRG1/Cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of NDRG1/Cap43 in the membrane.

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