World Journal of Surgery

, Volume 31, Issue 7, pp 1438–1444

Significance of CD44 Expression in Gastrointestinal Stromal Tumors in Relation to Disease Progression and Survival

  • Kai-Hsi Hsu
  • Hung-Wen Tsai
  • Yan-Shen Shan
  • Pin-Wen Lin
Article

Abstract

Background

CD44 is a transmembrane glycoprotein belonging to the cell-adhesion molecule family. It has been identified as being involved in tumor progression and metastasis, and its expression has been found to be of prognostic significance in several human malignancies. The aim of this study was to assess CD44 expression in gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumor of the gastrointestinal tract.

Methods

Between January 1995 and March 2006, 92 patients undergoing surgical resection for GIST in National Cheng Kung University Hospital were evaluated. To study the significance of CD44 expression, immunohistochemical staining of CD44 in tumor specimens was performed, and the clinicopathological information of patients was reviewed.

Results

Fifty-nine of 81 patients (73%) showed positive CD44 expression. Loss of CD44 expression was associated with disease progression (p = 0.019). Kaplan-Meier analysis revealed better progression-free survival among patients with strong CD44 expression (++ and +++) (p = 0.034), absence of disease progression (p < 0.001), and lower risk, according to National Institutes of Health (NIH) Consensus Criteria for GIST risk stratification (p = 0.003). Multivariate analysis demonstrated that high-risk status was the only independent risk factor for disease progression and the only independent predictor for a poor progression-free survival (p = 0.023 and 0.045, respectively).

Conclusions

It is demonstrated that high-risk status by NIH criteria is significantly associated with disease progression and poor progression-free survival in GIST.

References

  1. 1.
    Screaton GR, Bell MV, Jackson DG, et al. (1992) Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci USA 89:12160–12164PubMedCrossRefGoogle Scholar
  2. 2.
    Trowbridge I, Lesley J, Schulte R, et al. (1982) Biochemical characterization and cellular distribution of a polymorphic, murine cellsurface glycoprotein expressed in lymphoid tissues. Immunogenetics 15:299–312PubMedCrossRefGoogle Scholar
  3. 3.
    Naor D, Sionov RV, Ish-Shalom D. (1997) CD44: structure, function, and association with the malignant process. Adv Cancer Res 71:241–319PubMedGoogle Scholar
  4. 4.
    Tolg C, Hoffman M, Herrlich P, et al. (1993) Splicing choice from ten variant exons establishes CD44 variability. Nucleic Acid Res 21:1225–1229PubMedCrossRefGoogle Scholar
  5. 5.
    Soukka T, Salmi M, Joensuu H, et al. (1997) Regulation of CD44v6-containing isoforms during proliferation of normal and malignant epithelial cells. Cancer Res 57:2281–2289PubMedGoogle Scholar
  6. 6.
    Aruffo A, Stamenkovic I, Melnick M, et al. (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61:1303–1313PubMedCrossRefGoogle Scholar
  7. 7.
    Marhaba R, Zoller M (2004) CD44 in cancer progression: adhesion, migration and growth regulation. J Mol Histol 35:211–231PubMedCrossRefGoogle Scholar
  8. 8.
    Sneath RJ, Mangham DC (1998) The normal structure and function of CD44 and its role in neoplasia. Mol Pathol 51:191–200PubMedCrossRefGoogle Scholar
  9. 9.
    Gunthert U, Hofmann M, Rudy W, et al. (1991) A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65:13–24PubMedCrossRefGoogle Scholar
  10. 10.
    Granberg D, Wilander E, Oberg K, et al. (1999) Decreased survival in patients with CD44-negitive typical bronchial carcinoid tumors. Int J Cancer 84:484–488PubMedCrossRefGoogle Scholar
  11. 11.
    Humphrey G, Hazel DL, MacLennan K, et al. (1999) Expression of CD44 by rhabdomyosarcoma: a new prognostic marker? Br J Cancer 80:918–921PubMedCrossRefGoogle Scholar
  12. 12.
    Kahara N, Ozaki T, Doi T, et al. (2000) CD44 expression in soft tissue sarcomas. Virchows Arch 436:574–578PubMedCrossRefGoogle Scholar
  13. 13.
    Poncelet C, Walker F, Madelenat P, et al. (2001) Expression of CD44 standard and isoforms V3 and V6 in uterine smooth muscle tumors: a possible diagnostic tool for the diagnosis of leiomyosarcoma. Hum Pathol 32:1190–1196PubMedCrossRefGoogle Scholar
  14. 14.
    Peiper M, Sato T, Zurakowski D (2004) CD44s expression is associated with improved survival in soft tissue sarcoma. Anticancer Res 24:1053–1056PubMedGoogle Scholar
  15. 15.
    Diaz LK, Zhou X, Wright ET, et al. (2005) CD44 expression is associated with increased survival in node-negative invasive breast carcinoma. Clin Cancer Res 11:3309–3314PubMedCrossRefGoogle Scholar
  16. 16.
    Lai CH, Shan YS, Sy ED, et al. (2005) The significance of CD44 expression in gastrointestinal neuroendocrine tumors. Hepatogastroenterology 52:1071–1076PubMedGoogle Scholar
  17. 17.
    Kindblom LG, Remotti HE, Aldenborg F, et al. (1998) Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259–1269PubMedGoogle Scholar
  18. 18.
    Hirota S, Isozaki K, Moriyama Y, et al. (1998) Gain-of-function mutations of c-KIT in human gastrointestinal stromal tumors. Science 279:577–580PubMedCrossRefGoogle Scholar
  19. 19.
    Demetri GD, Mehren MV, Blanke CD, et al. (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480PubMedCrossRefGoogle Scholar
  20. 20.
    Savage DG, Antman KH (2002) Imatinib mesylate—a new oral targeted therapy. N Engl J Med 346:683–693PubMedCrossRefGoogle Scholar
  21. 21.
    Rubin BP, Singer S, Tsao C, et al. (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61:8118–8121PubMedGoogle Scholar
  22. 22.
    Roberts PJ, Eisenberg B (2002) Clinical presentation of gastrointestinal stromal tumors and treatment of operable disease. Eur J Cancer 38:S37–S38PubMedCrossRefGoogle Scholar
  23. 23.
    Nilsson B, Bumming P, Meis-Kindblom JM, et al. (2005) Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era–a population-based study in western Sweden. Cancer 103:821–829PubMedCrossRefGoogle Scholar
  24. 24.
    Iesalnieks I, Rummele P, Dietmaier W, et al. (2005) Factors associated with disease progression in patients with gastrointestinal stromal tumors in the pre-imatinib era. Am J Clin Pathol 124:740–748PubMedCrossRefGoogle Scholar
  25. 25.
    Fletcher CD, Berman JJ, Corless C, et al. (2002) Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 33:459–465PubMedCrossRefGoogle Scholar
  26. 26.
    Mazur MT, Clark HB (1983) Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol 7:507–519PubMedCrossRefGoogle Scholar
  27. 27.
    Ropponen KM, Eskelinen MJ, Lipponen PK, et al. (1998) Expression of CD44 and variant proteins in human colorectal cancer and its relevance for prognosis. Scand J Gastroenterol 33:301–309PubMedCrossRefGoogle Scholar
  28. 28.
    Wielenga VJ, van der Neut R, Offerhaus GJ, et al. (2000) CD44 glycoproteins in colorectal cancer: expression, function, and prognostic value. Adv Cancer Res 77:169–187PubMedCrossRefGoogle Scholar
  29. 29.
    Bankfalvi A, Terpe HJ, Breukelmann D, et al. (1998) Gains and losses of CD44 expression during breast carcinogenesis and tumour progression. Histopathology 33:107–116PubMedCrossRefGoogle Scholar
  30. 30.
    Sun X, Gong Y, Talamonti MS, et al. (2002) Expression of cell adhesion molecule, CD44s and E-cadherin, and microvessel density in carcinoid tumors. Modern Pathol 15:1333–1338CrossRefGoogle Scholar
  31. 31.
    Montgomery E, Abraham SC, Fisher C, et al. (2004) CD44 loss in gastric stromal tumors as a prognostic marker. Am J Surg Pathol 28:168–177PubMedCrossRefGoogle Scholar
  32. 32.
    Sugino T, Gorham H, Yoshida K, et al. (1996) Progressive loss of CD44 gene expression in invasive bladder cancer. Am J Pathol 149:873–882PubMedGoogle Scholar
  33. 33.
    Okamoto I, Tsuiki H, Kenyon LC, et al. (2002) Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. Am J Pathol 160:441–447PubMedGoogle Scholar
  34. 34.
    Heinrich MC, Corless CL (2005) Gastric GI stromal tumors (GISTs): the role of surgery in the era of targeted therapy. J Surg Oncol 90:195–207PubMedCrossRefGoogle Scholar
  35. 35.
    Yan H, Marchettini P, Acherman YI, et al. (2003) Prognostic assessment of gastrointestinal stromal tumor. Am J Clin Oncol 26:221–228PubMedCrossRefGoogle Scholar
  36. 36.
    Kwon SJ (2001) Korean Gastric Cancer Study Group. Surgery and prognostic factors for gastric stromal tumor. World J Surg 25:290–295PubMedCrossRefGoogle Scholar
  37. 37.
    Steinert DM, Oyarzo M, Wang X, et al. (2006) Expression of Bcl-2 in gastrointestinal stromal tumors correlation with progression-free survival in 81 patients treated with Imatinib Mesylate. Cancer 106:1617–1623PubMedCrossRefGoogle Scholar
  38. 38.
    Stewart AE, Heslin MH, Arch J, et al. (2006) Cyclooxygenase-2 expression and clinical outcome in gastrointestinal stromal tumors. J Gastrointest Surg 10:315–319PubMedCrossRefGoogle Scholar
  39. 39.
    Takahashi R, Tanaka S, Kitadai Y, et al. (2003) Expression of vascular endothelial growth factor and angiogenesis in gastrointestinal stromal tumor of the stomach. Oncology 64:266–274PubMedCrossRefGoogle Scholar
  40. 40.
    Dei Tos AP (2003) The reappraisal of gastrointestinal stromal tumors: from stout to the KIT revolution. Virchows Arch 442:421–428PubMedGoogle Scholar
  41. 41.
    Rudolph P, Gloeckner K, Parwaresch R, et al. (1998) Immunophenotype, proliferation, DNA-ploidy, and biological behavior of gastrointestinal stromal tumors: a multivariate clinicopathological study. Hum Pathol 29:791–800PubMedCrossRefGoogle Scholar
  42. 42.
    Singer S, Rubin BP, Lux ML, et al. (2002) Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol 20:3898–3905PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2007

Authors and Affiliations

  • Kai-Hsi Hsu
    • 1
  • Hung-Wen Tsai
    • 2
  • Yan-Shen Shan
    • 3
  • Pin-Wen Lin
    • 3
  1. 1.Department of SurgeryTainan Hospital, Department of Health, Executive Yuan, and Institute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityTainanTaiwan
  2. 2.Department of PathologyNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan
  3. 3.Department of SurgeryNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan

Personalised recommendations