Skip to main content Accessibility help

Expression of CD44 variant isoforms, CD44v3 and CD44v6, are associated with prognosis in nasopharyngeal carcinoma

  • K Sagawa (a1), N Uwa (a1), T Daimon (a2), M Sakagami (a1) and T Tsujimura (a3)...

The clinical and prognostic significance of CD44 variant isoform expression in nasopharyngeal carcinoma is not well known. This study aimed to clarify whether CD44 variant isoform expression serves as a prognostic factor in nasopharyngeal carcinoma.


Forty-two nasopharyngeal carcinoma patients, who underwent concurrent chemoradiotherapy as the initial treatment, were the subjects of investigation. Expression of CD44 variant isoforms, CD44v3, CD44v4, CD44v5, CD44v6 and CD44v7, in nasopharyngeal carcinoma was assessed in relation to concurrent chemoradiotherapy resistance and disease-specific survival of the patients.

Results and conclusion:

The patients with CD44v6 high expression showed a clinically incomplete response to concurrent chemoradiotherapy at the primary site. The disease-specific survival rate was lower in patients with high expression of CD44v3 than in those with low expression. These results suggest that analysis of CD44v6 and CD44v3 expression is useful in estimating prognosis and determining effective treatment strategies in nasopharyngeal carcinoma.

Corresponding author
Address for correspondence: Dr Nobuhiro Uwa, Department of Otorhinolaryngology – Head and Neck Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan Fax: +81 798 41 8976 E-mail:
Hide All

Presented at the 117th Annual Meeting of the American Academy of Otolaryngology –Head and Neck Surgery, 29 September – 2 October 2013, Vancouver, Canada.

Hide All
1 Kwong, DL, Sham, JS, Au, GK, Chua, DT, Kwong, PW, Cheng, AC et al. Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. J Clin Oncol 2004;22:2643–53
2 Liu, MT, Hsieh, CY, Chang, TH, Lin, JP, Huang, CC, Wang, AY. Prognostic factors affecting the outcome of nasopharyngeal carcinoma. Jpn J Clin Oncol 2003;33:50–8
3 Ponta, H, Sherman, I, Herrlich, PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003;4:3345
4 Goodison, S, Urquidi, V, Tarin, D. CD44 cell adhesion molecules. Mol Pathol 1999;52:189–96
5 Kalish, ED, Iida, N, Moffat, FL, Bourguignon, LY. A new CD44V3-containing isoform is involved in tumor cell growth and migration during human breast carcinoma progression. Front Biosci 1999;4:A1–8
6 Iida, N, Bourguignon, LY. New CD44 splice variants associated with human breast cancers. J Cell Physiol 1995;162:127–33
7 Ni, HM, Leong, AF, Cheong, D, Hooi, SC. Expression of CD44 variants in colorectal carcinoma quantified by real-time reverse transcriptase-polymerase chain reaction. J Lab Clin Med 2002;139:5965
8 Kuhn, S, Koch, M, Nübel, T, Ladwein, M, Antolovic, D, Klingbeil, P et al. A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression. Mol Cancer Res 2007;5:553–67
9 Lee, SC, Harn, HJ, Lin, TS, Yeh, KT, Liu, YC, Tsai, CS et al. Prognostic significance of CD44v5 expression in human thymic epithelial neoplasms. Ann Thorac Surg 2003;76:213–18
10 Handorean, AM, Yang, K, Robbins, EW, Flaig, TW, Iczkowski, KA. Silibinin suppresses CD44 expression in prostate cancer cells. Am J Transl Res 2009;1:80–6
11 Wang, SJ, Wong, G, de Heer, AM, Xia, W, Bourguignon, LY. CD44 variant isoforms in head and neck squamous cell carcinoma progression. Laryngoscope 2009;119:1518–30
12 Kunishi, M, Kayada, Y, Yoshiga, K. Down-regulated expression of CD44 variant 6 in oral squamous cell carcinoma and its relationship to regional lymph node metastasis. Int J Oral Maxillofac Surg 1997;26:280–3
13 Tsuruoka, S, Matsuo, K, Ishikawa, A, Yamamoto, N, Yamashita, Y, Takahashi, T. Prognostic significance of CD44v3 and CD44v6 in oral squamous cell carcinoma of the tongue. Oral Med Pathol 2011;15:1012
14 Uwa, N, Kataoka, TR, Torii, I, Sato, A, Nishigami, T, Song, M et al. CD44 expression is related to poor prognosis of hypopharyngeal squamous cell carcinoma. Acta Otolaryngol 2011;131:32–9
15 R Core Team. R: A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing
16 Sobin, LH, Gospodarowicz, MK, Wittekind, C. TNM Classification of Malignant Tumours. Hoboken, NJ: Wiley-Blackwell, 2009
17 Bourguignon, LY, Gilad, E, Brightman, A, Diedrich, F, Singleton, P. Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+ signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells. J Biol Chem 2006;281:14026–40
18 Wang, SJ, Bourguignon, LY. Hyaluronan and the interaction between CD44 and epidermal growth factor receptor in oncogenic signaling and chemotherapy resistance in head and neck cancer. Arch Otolaryngol Head Neck Surg 2006;132:771–8
19 Trachootham, D, Alexandre, J, Huang, P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 2009;8:579–91
20 Diehn, M, Cho, RW, Lobo, NA, Kalisky, T, Dorie, MJ, Kulp, AN et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009;458:780–3
21 Gottesman, MM, Fojo, T, Bates, SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002;2:4858
22 Prince, ME, Sivanandan, R, Kaczorowski, A, Wolf, GT, Kaplan, MJ, Dalerba, P et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 2007;104:973–8
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The Journal of Laryngology & Otology
  • ISSN: 0022-2151
  • EISSN: 1748-5460
  • URL: /core/journals/journal-of-laryngology-and-otology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed