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, log in via an institution to check access.
Similar content being viewed by others
References
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
Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003;4:33–45
Sneath RJ, Mangham DC. The normal structure and function of CD44 and its role in neoplasia. Mol Pathol 1998;51:191–200
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
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
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
Stauder R, Van Driel M, Schwarzler C, et al. Different CD44 splicing patterns define prognostic subgroups in multiple myeloma. Blood 1996;88:3101–8
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
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
Goodison S, Urquidi V, Tarin D. CD44 cell adhesion molecules. Mol Pathol 1999;52:189–96
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
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
Yun KJ YK, Han WC. Immunohistochemical study for CD44v6 in hepatocellular carcinoma and cholangiocarcinoma. Cancer Res Treat 2002;34:170–4
Naor D, Nedvetzki S, Golan I, et al. CD44 in cancer. Crit Rev Clin Lab Sci 2002;39:527–79
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
Nagano O, Saya H. Mechanism and biological significance of CD44 cleavage. Cancer Sci 2004;95:930–5
Yanagisawa N, Mikami T, Mitomi H, et al. CD44 variant overexpression in gallbladder carcinoma associated with tumor dedifferentiation. Cancer 2001;91:408–16
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
Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 1996;224:463–73
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
Acknowledgment
Supported by an intramural research grant (year 2004) of Ewha Womans University.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-007-9786-9