Clinical Significance of Dysadherin Expression in Gastric Cancer Patients

Yutaka Shimada, Seiji Yamasaki, Yosuke Hashimoto, Tetsuo Ito, Jun Ichiro Kawamura, Toshiya Soma, Yoshinori Ino, Yukihiro Nakanishi, Michiie Sakamoto, Setsuo Hirohashi, Masayuki Imamura

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Abstract

Purpose: Dysadherin, a cancer-associated cell membrane glycoprotein, has been reported to down-regulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in gastric cancer, we examined dysadherin and E-cadherin expression in gastric cancer patients. Experimental Design: Dysadherin and E-cadherin expression were evaluated in 276 gastric cancer patients by immunohistochemistry, and the results were compared with the clinicopathological findings of the subjects. Results: Dysadherin was not expressed in normal gastric epithelium. Both dysadherin and E-cadherin were localized to the cell membrane. Dysadherin expression was sometimes largely localized to infiltrating tumor cells or cells dissociating. Ninety gastric cancer patients (32.6%) were positive for dysadherin, and 151 patients (54.7%) showed preservation of E-cadherin expression. Expression of dysadherin was associated with moderately differentiated carcinoma and hematogenous metastasis, whereas reduced expression of E-cadherin showed an association with poorly differentiated carcinoma and peritoneal dissemination. As a result, dysadherin positivity and reduced E-cadherin expression were associated with a poor prognosis. In addition, patients with both dysadherin positivity and reduced E-cadherin had the worst prognosis. Multivariate analysis revealed that reduced E-cadherin expression was an independent prognostic factor, but dysadherin expression was not. Conclusion: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis and the mode of metastasis in gastric cancer patients. Patients with dysadherin positivity have a higher risk of hematogenous metastasis, whereas patients with reduced E-cadherin expression have an increased risk of peritoneal dissemination.

Original languageEnglish
Pages (from-to)2818-2823
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number8
DOIs
Publication statusPublished - 2004 Apr 15

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Shimada, Y., Yamasaki, S., Hashimoto, Y., Ito, T., Kawamura, J. I., Soma, T., Ino, Y., Nakanishi, Y., Sakamoto, M., Hirohashi, S., & Imamura, M. (2004). Clinical Significance of Dysadherin Expression in Gastric Cancer Patients. Clinical Cancer Research, 10(8), 2818-2823. https://doi.org/10.1158/1078-0432.CCR-0633-03