Claudin-3 and claudin-4 expression in serous papillary, clear-cell, and endometrioid endometrial cancer

Gottfried E. Konecny, Rachana Agarwal, Gary A. Keeney, Boris Winterhoff, Monica Brown Jones, Andrea Mariani, Darren Riehle, Christina Neuper, Sean C. Dowdy, He Jing Wang, Patrice J. Morin, Karl C. Podratz

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56 Scopus citations

Abstract

Objective: Tight junction (TJ) proteins claudin-3 and claudin-4 may be differentially expressed in uterine serous papillary carcinoma (USPC), a rare form of endometrial cancer characterized by a particularly poor prognosis. Our aim was to determine the expression pattern and prognostic relevance of claudin-3 and claudin-4 in a large cohort of endometrial cancer patients of diverse histological type and stage. Methods: Claudin-3 and claudin-4 expression was studied in a cohort of 287 patients with endometrial cancer including 137 cases of USPC or clear-cell histology using immunohistochemistry. Patients were completely surgically staged. Outcome data is available on all 287 patients. Results: The rate of claudin-3 and claudin-4 expression was significantly higher in USPC and clear-cell endometrial cancer compared to endometrioid endometrial cancer (claudin-3: 78% and 61% versus 38%, p < .0001; claudin-4: 56% and 44% versus 9%, p < .0001). Furthermore, expression of both TJ proteins was significantly associated with poor clinical outcome (claudin-3, DFS RR 1.70, p = .0087, OS RR 1.62, p = .0247; claudin-4, DFS RR 2.66, p < 0.0001, and OS RR 2.50, p < 0.0001). However, both markers did not maintain prognostic independence in multivariate analyses, as their expression was tightly associated with more advanced disease stages (p < .0001 for both), and higher nuclear grade (p < .0001 for both). Conclusion: These clinical observations confirm the hypothesis based on preclinical evidence that increased expression of claudin-3 and claudin-4 may contribute to the aggressive phenotype of endometrial cancer of serous papillary or clear-cell histology and suggest their potential utility as diagnostic biomarkers and possible targets for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)263-269
Number of pages7
JournalGynecologic oncology
Volume109
Issue number2
DOIs
StatePublished - May 2008

Keywords

  • Claudin-3
  • Claudin-4
  • Endometrial
  • Uterine serous papillary endometrial cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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    Konecny, G. E., Agarwal, R., Keeney, G. A., Winterhoff, B., Jones, M. B., Mariani, A., Riehle, D., Neuper, C., Dowdy, S. C., Wang, H. J., Morin, P. J., & Podratz, K. C. (2008). Claudin-3 and claudin-4 expression in serous papillary, clear-cell, and endometrioid endometrial cancer. Gynecologic oncology, 109(2), 263-269. https://doi.org/10.1016/j.ygyno.2008.01.024