Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness: Relationship to E-cadherin expression

Takeshi Shimamura, Michiie Sakamoto, Yoshinori Ino, Yasuto Sato, Kazuaki Shimada, Tomoo Kosuge, Hisahiko Sekihara, Setsuo Hirohashi

研究成果: Article査読

75 被引用数 (Scopus)

抄録

Purpose: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, we reported the cloning and characterization of dysadherin and showed that it downregulated E-cadherin and promoted metastasis. The aim of this study was to investigate the clinical significance of dysadherin expression and the relationship between dysadherin expression and E-cadherin expression in pancreatic ductal adenocarcinoma. Patients and Methods: We examined dysadherin and E-cadherin expression in 125 surgically resected pancreatic ductal adenocarcinoma patients using immunohistochemistry. Results: Dysadherin was expressed at the cell membrane of cancer cells, but not in nontumor duct and acinar cells. Its expression was stronger in infiltrative and poorly differentiated nests compared with well-differentiated nests. Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. Increased dysadherin expression was significantly correlated with distant metastasis (P = .047), high tumor grade (P = .006), positive tumor margins (P = .024), and infiltrative type of growth pattern (P = .014). A survival advantage was observed in patients with 0% to 20% dysadherin-positive cells compared with patients with 51% to 100% dysadherin-positive cells, independent of tumor-node-metastasis classification, and World Health Organization tumor grade (P = .019). A combination of increased dysadherin expression and reduced E-cadherin expression (< 90%) further worsened the prognosis. Conclusion: In pancreatic ductal adenocarcinoma, dysadherin expression seems to reflect tumor aggressiveness and to be a positive marker of poor prognosis when considered both alone and in combination with downregulation of E-cadherin.

本文言語English
ページ(範囲)659-667
ページ数9
ジャーナルJournal of Clinical Oncology
21
4
DOI
出版ステータスPublished - 2003 2月 15
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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