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Medical Oncology

, Volume 20, Issue 3, pp 255–263 | Cite as

The CD44 receptor is a molecular predictor of survival in ovarian cancer

  • L. Rodríguez-Rodríguez
  • I. Sancho-Torres
  • C. Mesonero
  • D. G. Gibbon
  • W. J. Shih
  • G. Zotalis
Original Article

Abstract

Purpose: CD44 is a cell surface receptor implicated in cancer progression and metastases. Malignant tumors may show a loss of CD44 splice control mechanisms. We investigated the role of CD44 splice variant expression in ovarian tumors and metastases, and its association with survival.

Experimental Design: We tested CD44 expression in 142 cases of epithelial carcinoma of the ovary and 265 metastatic sites by immunohistochemistry.

Results: Survival analysis showed that the expression of CD44s, CD44-v4,-v5, -v6, -v9, and -v10 are significant predictors for survival in univariate analysis. After stage, the expression of CD44-v10 in metastases was the strongest predictor of decreased survival in multivariate analysis (p=0.0009). Conversely, CD44-v10 expression in the primary tumor was an independent predictor of improved survival in multivariate analysis (p=0.0002). The expression of CD44s in the tumor/stroma interface of the primary tumor was associated with improved survival (p<0.0001).

Conclusions: CD44 variant expression is a molecular prognostic maker for epithelial ovarian carcinomas. CD44-v10 expression is an independent prognostic indicator and the site of expression determines a positive or negative influence in survival. Our results also indicate that CD44 may be involved in important tumor/stroma interactions.

Key Words

CD44 metastases tumor stroma ovarian cancer proliferation invasion 

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References

  1. 1.
    Kohn EC, Liotta LA. Molecular insights into cancer invasion: Strategies for prevention and intervention. Cancer Res 1995; 55:1856–1862.PubMedGoogle Scholar
  2. 2.
    Lee TH, Wisniewski HG, Vilcek J. A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44. J Cell Biol 1992; 116:545–557.PubMedCrossRefGoogle Scholar
  3. 3.
    Levesque MC, Haynes BF, TNFα and IL-4 regulation of hyaluronan binding to monocyte CD44 involves posttranslational modification of CD44. Cellular Immunology 1999; 193:209–218.PubMedCrossRefGoogle Scholar
  4. 4.
    Gardner MJ, Jones L, Catterall J, Turner G. Expression of cell adhesion molecules on ovarian tumor cell lines and mesothelial cells in relation to ovarian cancer metastasis. Cancer Lett 1995; 91:229–234.PubMedCrossRefGoogle Scholar
  5. 5.
    Chiu RK, et al. Alternatively spliced CD44 isoforms containing exon v10 promote cellular adhesion through the recognition of chondroitin sulfate-modified CD44. Experim Cell Res 1999; 248:213–321.Google Scholar
  6. 6.
    Goodison S, Tarin D. Current status of CD44 variant isoforms as cancer diagnostic markers. Histopathology 1998; 32:1–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Rodríguez-Rodríguez L, et al. CD44 splice variant expression in clear cell carcinoma of the ovary. Gynecol Oncol 1998; 71:223–229.PubMedCrossRefGoogle Scholar
  8. 8.
    Darai E, et al. Analysis of CD44 expression in serous and mucinous borderline tumours of the ovary: Comparison with cystadenomas and overt carcinomas. Histopathology 1998; 32:151–159.PubMedCrossRefGoogle Scholar
  9. 9.
    Ross JS, et al. Decreased CD44 standard form expression correlates with prognostic variables in ovarian carcinomas. Am J Clin Pathol 2001; 116:122–128.PubMedCrossRefGoogle Scholar
  10. 10.
    Sancho-Torres I, Mesonero C, Miller-Watelet JL, Gibbon DG, Rodríguez-Rodríguez L. Clear cell carcinoma of the ovary. Characterization of its CD44 isoform repertoire. Gynecol Oncol 2000; 79:187–195.PubMedCrossRefGoogle Scholar
  11. 11.
    Gibbon DG, et al. CD44 splice variants expression correlates with in vitro mestastatic potential in ovarian cancer cell lines. J Soc Gynecol Invest 1998; 5:82A-83A.CrossRefGoogle Scholar
  12. 12.
    Saegusa M, Machida D, Hashimura M, Okayasu I. CD44 expression in benign, pemalignant, and malignant ovarian neoplasms: Relation to tumour development and progression. J Pathol 1999; 189:326–337.PubMedCrossRefGoogle Scholar
  13. 13.
    Mackay CR, et al. Expression and modulation of CD44 variant isoforms in humans. J Cell Biol 1994; 124:71–82.PubMedCrossRefGoogle Scholar
  14. 14.
    Rösel M, Khaldoyanidi S, Zawadzki V, Zoller M. Involvement of CD44 variant isoform v10 in progenitor cell adhesion and maturation. Exp Hematol 1999; 27:698–711.PubMedCrossRefGoogle Scholar
  15. 15.
    Iida N, Bourguignon LY. Coexpression of CD44 variant (v10/ex14) and CD44s in human mammary epithelial cells promotes tumorigenesis. J Cell Physiol 1997; 171:152–160.PubMedCrossRefGoogle Scholar
  16. 16.
    Cannistra SA, De Franzo B, Niloff J., Ottensmeier C. Functional heterogeneity of CD44 molecules in ovarian cancer cells. Clin Cancer Res 1995; 1:333–342.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • L. Rodríguez-Rodríguez
    • 1
  • I. Sancho-Torres
    • 2
  • C. Mesonero
    • 3
  • D. G. Gibbon
    • 1
  • W. J. Shih
    • 4
  • G. Zotalis
    • 3
  1. 1.Department of Obstetrics and GynecologyThe Cancer Institute of New Jersey, Division of Gynecologic Oncology, UMDNJ/Robert Wood Johnson Medical SchoolNew Brunswick
  2. 2.Department of Obstetrics and GynecologyStaten Island University HospitalStaten Island
  3. 3.University of Rochester Medical CenterRochester
  4. 4.The Cancer Institute of New Jersey, Division of BiometricsUMDNJ/ Robert Wood Johnson Medical SchoolNew Brunswick

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