Skip to main content

Prognostic Significance of CD44s Expression in Biliary Tract Cancers

Annals of Surgical Oncology volume 15, pages 1155–1160 (2008)Cite this article

Abstract

Background

CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers.

Methods

Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed.

Results

Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37–86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211–.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630–3.393; P = .377) had no prognostic significance for survival.

Conclusions

CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Choi YL, Xuan YH, Shin YK, et al. An immunohistochemical study of the expression of adhesion molecules in gallbladder lesions. J Histochem Cytochem 2004;52:591–601

    PubMed  CAS  Google Scholar 

  2. Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003;4:33–45

    PubMed  Article  CAS  Google Scholar 

  3. Sneath RJ, Mangham DC. The normal structure and function of CD44 and its role in neoplasia. Mol Pathol 1998;51:191–200

    PubMed  CAS  Google Scholar 

  4. Kawano T, Nakamura Y, Yanoma S, et al. Expression of E-cadherin, and CD44s and CD44v6 and its association with prognosis in head and neck cancer. Auris Nasus Larynx 2004;31:35–41

    PubMed  Article  Google Scholar 

  5. Nihei Z, Ichikawa W, Kojima K, et al. The positive relationship between the expression of CD44 variant 6 and prognosis in colorectal cancer. Surg Today 1996;26:760–1

    PubMed  Article  CAS  Google Scholar 

  6. Nishimura S, Chung YS, Yashiro M, et al. CD44H plays an important role in peritoneal dissemination of scirrhous gastric cancer cells. Jpn J Cancer Res 1996;87:1235–44

    PubMed  CAS  Google Scholar 

  7. Stauder R, Van Driel M, Schwarzler C, et al. Different CD44 splicing patterns define prognostic subgroups in multiple myeloma. Blood 1996;88:3101–8

    PubMed  CAS  Google Scholar 

  8. Tempfer C, Losch A, Heinzl H, et al. Prognostic value of immunohistochemically detected CD44 isoforms CD44v5, CD44v6 and CD44v7–8 in human breast cancer. Eur J Cancer 1996;32A:2023–5

    PubMed  Article  CAS  Google Scholar 

  9. Stavropoulos NE, Filliadis I, Ioachim E, et al. CD44 standard form expression as a predictor of progression in high risk superficial bladder tumors. Int Urol Nephrol 2001;33:479–83

    PubMed  Article  CAS  Google Scholar 

  10. Goodison S, Urquidi V, Tarin D. CD44 cell adhesion molecules. Mol Pathol 1999;52:189–96

    PubMed  CAS  Article  Google Scholar 

  11. Kalekou H, Miliaras D. Immunohistochemical study of microvessel density, CD44 (standard form), p53 protein and c-erbB2 in gallbladder carcinoma. J Gastroenterol Hepatol 2004;19:812–8

    PubMed  Article  Google Scholar 

  12. Mikami T, Saegusa M, Mitomi H, et al. Significant correlations of E-cadherin, catenin, and CD44 variant form expression with carcinoma cell differentiation and prognosis of extrahepatic bile duct carcinomas. Am J Clin Pathol 2001;116:369–76

    PubMed  Article  CAS  Google Scholar 

  13. Yun KJ YK, Han WC. Immunohistochemical study for CD44v6 in hepatocellular carcinoma and cholangiocarcinoma. Cancer Res Treat 2002;34:170–4

    Google Scholar 

  14. Naor D, Nedvetzki S, Golan I, et al. CD44 in cancer. Crit Rev Clin Lab Sci 2002;39:527–79

    PubMed  Article  CAS  Google Scholar 

  15. Sugino T, Gorham H, Yoshida K, et al. Progressive loss of CD44 gene expression in invasive bladder cancer. Am J Pathol 1996;149:873–82

    PubMed  CAS  Google Scholar 

  16. Nagano O, Saya H. Mechanism and biological significance of CD44 cleavage. Cancer Sci 2004;95:930–5

    PubMed  Article  CAS  Google Scholar 

  17. Yanagisawa N, Mikami T, Mitomi H, et al. CD44 variant overexpression in gallbladder carcinoma associated with tumor dedifferentiation. Cancer 2001;91:408–16

    PubMed  Article  CAS  Google Scholar 

  18. Faivre J, Forman D, Esteve J, et al. Survival of patients with primary liver cancer, pancreatic cancer and biliary tract cancer in Europe. Eur J Cancer 1998;34:2184–90

    Article  CAS  Google Scholar 

  19. Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 1996;224:463–73

    PubMed  Article  CAS  Google Scholar 

  20. Yokoyama Y, Hiyama E, Murakami Y, et al. Lack of CD44 variant 6 expression in advanced extrahepatic bile duct/ampullary carcinoma. Cancer 1999;86:1691–9

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgment

Supported by an intramural research grant (year 2004) of Ewha Womans University.

Author information

Affiliations

  1. Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Ewha Medical Research Center, Ewha Womans University, Mock-Dong 911-1, Yangchun-ku, Seoul, 158-710, Korea

    Sang Min Lee MD, Kyoung Eun Lee MD, PhD, Hye Jung Chang MD, Moon Young Choi MD, Yeung Chul Mun MD, PhD, Eun Mi Nam MD, PhD, Chu Myong Seong MD & Soon Nam Lee MD, PhD

  2. Department of Pathology, School of Medicine, Ewha Medical Research Center, Ewha Womans University, Mock-Dong 911-1, Yangchun-ku, Seoul, 158-710, Korea

    Min-Sun Cho MD, PhD

  3. Department of Surgery, School of Medicine, Ewha Medical Research Center, Ewha Womans University, Mock-Dong 911-1, Yangchun-ku, Seoul, 158-710, Korea

    Seog Ki Min MD, PhD & Hyeon Kook Lee MD, PhD

Authors
  1. Sang Min Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoung Eun Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hye Jung Chang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moon Young Choi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Min-Sun Cho MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seog Ki Min MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hyeon Kook Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yeung Chul Mun MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eun Mi Nam MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chu Myong Seong MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Soon Nam Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyoung Eun Lee MD, PhD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lee, S.M., Lee, K.E., Chang, H.J. et al. Prognostic Significance of CD44s Expression in Biliary Tract Cancers. Ann Surg Oncol 15, 1155–1160 (2008). https://doi.org/10.1245/s10434-007-9786-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-007-9786-9

Keywords

  • CD44s
  • CD44v6
  • Biliary tract cancer
  • Prognosis
  • Immunohistochemistry