Gastric Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 7, 2006; 12(5): 691-696
Published online Feb 7, 2006. doi: 10.3748/wjg.v12.i5.691
Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer
Pei-Hong Jiang, Yoshiharu Motoo, Stéphane Garcia, Juan Lucio Iovanna, Marie-Josèphe Pébusque, Norio Sawabu
Pei-Hong Jiang, Norio Sawabu, Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
Yoshiharu Motoo, Department of Medical Oncology, Kanazawa Medical University, Ishikawa, Japan
Stéphane Garcia, Juan Lucio Iovanna, Marie-Josèphe Pébusque, INSERM U624, Marseille, France
Correspondence to: Yoshiharu Motoo, MD, Department of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. motoo@kanazawa-med.ac.jp
Telephone: +81-76-218-8284 Fax: +81-76-218-8283
Received: May 30, 2005
Revised: May 30, 2005
Accepted: June 1, 2005
Published online: February 7, 2006
Abstract

AIM: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer.

METHODS: TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed.

RESULTS: TP53INP1 was expressed in 98% (139/142 cases) of non-cancerous gastric tissues and was down-expressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%). Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3% vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients). P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P = 0.0006).

CONCLUSION: TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may reflect the malignant grade of gastric cancer and is regarded as an adverse prognostic factor.

Keywords: Tumor protein 53-induced nuclear protein 1; p53; Gastric cancer