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

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)659-667
Number of pages9
JournalJournal of Clinical Oncology
Volume21
Issue number4
DOIs
Publication statusPublished - 2003 Feb 15
Externally publishedYes

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Cadherins
Adenocarcinoma
Neoplasms
Neoplasm Metastasis
Down-Regulation
Acinar Cells
Cell Adhesion
Organism Cloning
Immunohistochemistry
Cell Membrane
Survival
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness : Relationship to E-cadherin expression. / Shimamura, Takeshi; Sakamoto, Michiie; Ino, Yoshinori; Sato, Yasuto; Shimada, Kazuaki; Kosuge, Tomoo; Sekihara, Hisahiko; Hirohashi, Setsuo.

In: Journal of Clinical Oncology, Vol. 21, No. 4, 15.02.2003, p. 659-667.

Research output: Contribution to journalArticle

Shimamura, Takeshi ; Sakamoto, Michiie ; Ino, Yoshinori ; Sato, Yasuto ; Shimada, Kazuaki ; Kosuge, Tomoo ; Sekihara, Hisahiko ; Hirohashi, Setsuo. / Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness : Relationship to E-cadherin expression. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 4. pp. 659-667.
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abstract = "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.",
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T1 - Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness

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AU - Shimamura, Takeshi

AU - Sakamoto, Michiie

AU - Ino, Yoshinori

AU - Sato, Yasuto

AU - Shimada, Kazuaki

AU - Kosuge, Tomoo

AU - Sekihara, Hisahiko

AU - Hirohashi, Setsuo

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N2 - 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.

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