Gastric Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 28, 2006; 12(24): 3803-3809
Published online Jun 28, 2006. doi: 10.3748/wjg.v12.i24.3803
Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations
Kimiyasu Yamazaki, Yusuke Tajima, Reiko Makino, Nobukazu Nishino, Shigeo Aoki, Masanori Kato, Masaaki Sakamoto, Koji Morohara, Tsutomu Kaetsu, Mitsuo Kusano
Kimiyasu Yamazaki, Yusuke Tajima, Reiko Makino, Nobukazu Nishino, Shigeo Aoki, Masanori Kato, Masaaki Sakamoto, Koji Morohara, Tsutomu Kaetsu, Mitsuo Kusano, Department of Surgery, Division of General and Gastroenterological Surgery, Showa University, School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Reiko Makino, Clinical Research Laboratory, Showa University, School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
Author contributions: All authors contributed equally to the work.
Supported by Grant-in-Aid for Scientific Research, Japan Society for the Promotion of Science, No. 17790928
Correspondence to: Yusuke Tajima, Department of Surgery, Division of General and Gastroenterological Surgery, Showa University, School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku Tokyo 142-8666, Japan. surgery@med.showa-u.ac.jp
Telephone: +81-3-37848541 Fax: +81-3-37845835
Received: December 29, 2005
Revised: January 5, 2006
Accepted: January 14, 2006
Published online: June 28, 2006
Abstract

AIM: To clarify the relations between tumor differentiation phenotype and tumor invasion or genetic alterations in gastric differentiated-type tumors.

METHODS: We examined the tumor differentiation phenotype, the presence of mutations in APC and p53, and the microsatellite instability (MSI) status in 48 gastric adenomas and 171 differentiated-type carcinomas. The tumor differentiation phenotype was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10. The tumors were then classified into gastric- (G-), gastric and intestinal mixed- (GI-), or intestinal- (I-) phenotypes, according to the immunopositivity of the above markers. The presence of mutations in APC and p53 and the MSI status were also investigated in all the tumors.

RESULTS: Gastric adenomas were significantly associated with CD10 expression, I-phenotype tumors and the presence of APC mutations, compared with carcinomas (66.7% vs 25.1%, P < 0.0001; 56.3% vs 14.6%, P < 0.0001; 39.6% vs 14.0%, P < 0.0001, respectively) and inversely associated with expressions of HGM and MUC6 and the presence of p53 mutations (10.4% vs 62.6%, P < 0.0001; 39.6% vs 64.3%, P = 0.003; 2.0% vs 26.3%, P = 0.001, respectively). The frequency of APC mutations was significantly higher in HGM-negative tumors, MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors than in HGM-positive tumors, MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors (32.7% vs 7.1%, P < 0.0001; 27.8% vs 14.0%, P = 0.0182; 37.3% vs 10.4%, P < 0.0001; and 38.5% vs 9.5%, P = 0.0017, respectively). The frequency of MSI was significantly higher in MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors than in MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors (24.8% vs 6.7%, P = 0.0009; 22.2% vs 8.0%, P = 0.0143; and 28.6% vs 9.6%, P = 0.0353, respectively).

CONCLUSION: The tumor differentiation phenotype is closely related to tumor invasion and genetic alterations in gastric differentiated-type tumors.

Keywords: Gastric carcinoma, Tumor differentiation phenotype, APC, p53, Microsatellite instability