Abstract
In many malignant diseases the expression levels of CD44 and its splice variant v6 (CD44v6) have been associated with the prognosis. The purpose of this study was to investigate the clinical significance of CD44 in adult soft tissue sarcomas (STS). 133 STS patients with a limb or superficial trunk tumour treated at the Helsinki University Central Hospital in 1987–1993 with a median follow-up time of 68 months were included in this study. The expression of CD44 and CD44v6 was determined immunohistochemically on paraffin-embedded tumour samples. 95% of the tumours expressed CD44 and CD44v6 was detected in 57%. Strong CD44 expression was associated with low grade (P=0.04) and small tumour size (P=0.02). In diploid tumours the CD44 expression was correlated with low S-phase fraction (P=0.001). High expression of both, CD44 in general as well as that of CD44v6, predicted a higher risk for local recurrence (CD44: P=0.01 and CD44v6: P=0.05). Low CD44v6 content of the primary tumour correlated with poor survival (P=0.02). Determining the expression of CD44 or CD44v6 in a primary STS could be a valuable tool for selecting the group of patients who might benefit from intensified local tumour treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Aho R, Kalimo H, Salmi M, Smith D and Jalkanen S (1997) Binding of malignant lymphoid cells to the white matter of the human central nervous system: Role of different CD44 isoforms, β1, β2and β7integrins and L-selectin. J Neuropathol Exp Neurol 56: 557–568
Alvegård TA, Berg NO, Ranstam J, Rydholm A and Rooser B (1989) Prognosis in high-grade soft tissue sarcomas. The Scandinavian Sarcoma Group experience in a randomized adjuvant chemotherapy trial. Acta Orthop Scand 60: 517–521
Belitsos PC, Hilderth JEK and August JT (1990) Homotypic cell aggregation induced by anti-CD44 (Pgp-1) monoclonal antibodies and related to CD44 (Pgp-1) expression. J Immunol 144: 1661–1670
Collin C, Godbold J, Hajdu S and Brennan M (1987) Localized extremity soft tissue sarcoma: an analysis of factors affecting survival. J Clin Oncol 5: 601–612
Collin F, Chassevent A, Bonichon F, Bertrand G, Terrier P and Coindra JM (1997) Flow cytometric DNA content analysis of 185 soft tissue neoplasms indicates that S-phase fraction is a prognostic factor for sarcomas. French Federation of Cancer Centers (FNCLCC) Sarcoma Group. Cancer 79: 2371–2379
Choong PF, Åkerman M, Willen H, Andersson C, Gustafson P, Alvegård T and Rydholm A (1995) Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in soft tissue sarcoma. Is prognostic significance histotype-specific?. APMIS 103: 797–805
Denning SM, Le PT, Singer KH and Haynes BF (1990) Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation. J Immunol 144: 7–15
Dirix LY and Van Oosterom AT (1995) Diagnosis and treatment of soft tissue sarcomas in adults. Curr Opin Oncol 7: 340–348
Günthert U, Hofmann M, Rudy W, Reber S, Zoller M, Haussmann I, Matzku S, Wenzel A, Ponta H and Herrlich P (1991) A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65: 13–24
Herrlich P, Pals S and Ponta H (1995) CD44 in colon cancer. Eur J Cancer 31A: 1110–1112
Hong RL, Pu YS, Hsieh TS, Chu JS and Lee WJ (1995) Expressions of E-cadherin and exon v6-containing isoforms of CD44 and their prognostic values in human transitional cell carcinoma. J Urol 153: 2025–2028
Hudson DL, Speight, PM Watt FM (1996) Altered expression of CD44 isoforms in squamous-cell carcinomas and cell lines derived from them. Int J Cancer 66: 457–463
Huuhtanen RL, Blomqvist CP, Wiklund TA, Virolainen MJ, Elomaa AI, Pan Y and Tribukait B (1996) S-phase fraction of 155 soft tissue sarcomas: correlation with clinical outcome. Cancer 77: 1815–1822
Huuhtanen RL, Blomqvist CP, Wiklund TA, Böhling TO, Virolainen MJ, Tukiainen EJ, Tribukait B and Andersson LC (1999) Comparison of the Ki-67 score and S-phase fraction as prognostic variables in soft-tissue sarcoma. Br J Cancer 79: 945–951
Ishida T (2000) Immunohistochemical expression of the CD44 variant 6 in colorectal adenocarcinoma. Surg Today 30 ( 1): 28–32
Jacobson K, O'Dell D, Holifield B, Murphy TL and August JT (1984) Redistribution of a major cell surface glycoprotein during cell movement. J Cell Biol 99: 1613–1623
Jackson DG, Bell JI, Dickinson R, eTimans J, Shields J and Whittle N (1995) Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon. J Cell Biol 128: 673–685
Jalkanen S, Bargatze RF, Herron LR and Butcher EC (1986) A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man. Eur J Immunol 16: 1195–1202
Jalkanen S, Bargatze RF, de los Toyos J and Butcher EC (1987) Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85–95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells. J Cell Biol 105: 983–990
Kahana N, Ozaki T, Doi T, Nishida K, Kawai A, Shibahara M and Inoue H (2000) CD44 expression in soft tissue sarcomas. Virchows Arch 436: 574–578
Kainz C, Kohlberger P, Tempfer C, Sliutz G, Gitsch G, Reinthaller A and Breitenecker G (1995) Prognostic value of CD44 splice variants in human stage III cervical cancer. Eur J Cancer 31A: 1706–1709
Koopman G, Heider KH, Horst E, Adolf GR, van den Berg F, Ponta H, Herrlich P and Pals ST (1993) Activated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis – associated variant of CD44. J Exp Med 177: 897–904
Mackay CR, Terpe HJ, Stauder R, Marston WL, Stark H and Günthert U (1994) Expression and modulation of CD44 variant isoforms in humans. J Cell Biol 124: 71–82
Miyake K, Underhill CB, Lesley J and Kincade PW (1990a) Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med 172: 69–75
Miyake K, Medina KL, Hayashi S-I, Ono S, Hamaoka T and Kincade PW (1990b) Monoclonal antibodies to Pgp-1/CD44 block lymphohematopoiesis in long-term bone marrow cultures. J Exp Med 171: 477–488
Mulder JWR, Wielenga VJM, Polak MM, van den Bergh FM, Adolf GR, Herrlich P, Pals ST and Offerhaus GJ (1995) Expression of mutant p53 and CD44 variant proteins in colorectal tumorigenesis. Gut 36: 76–80
Naor D, Sionov R and Ish Shalom D (1997) CD44: structure, function, and association with the malignant process. Adv Cancer Res 71: 241–319
Picker LJ, Nakache M and Butcher EC (1989) Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol 109: 927–937
Ross JS, del Rosario AD, Bui HX, Kallakury BV, Okby NT and Figge J (1996) Expression of the CD44 cell adhesion molecule in urinary bladder transitional cell carcinoma. Mod Pathol 9: 854–860
Ruiz P, Schwarzler C and Günthert U (1995) CD44 isoforms during differentiation and development. Bioessays 17: 17–24
Rööser B, Attewell R, Berg NO and Rydholm A (1987) Survival in soft tissue sarcoma. Prognostic variables identified by multivariate analysis. Acta Orthop Scand 58: 516–522
Seelentag WK, Günthert U, Saremaslani P, Futo E, Pfaltz M, Heitz PU and Roth J (1996) CD44 standard and variant isoform expression in human epidermal skin tumors is not correlated with tumor aggressiveness but down-regulated during proliferation and tumor de-differentiation. Int J Cancer 69: 457–463
Soukka T, Salmi M, Joensuu H, Häkkinen L, Sointu P, Koulu L, Kalimo K, Klemi P, Grenman R and Jalkanen S (1997) Regulation of CD44v6-containing isoforms during proliferation of normal and malignant epithelial cells. Cancer Res 57: 2281–2289
Sugino T, Gorham H, Yoshida K, Bolodeoku J, Nargund V, Cranston D, Goodison S and Tarin D (1996) Progressive loss of CD44 gene expression in invasive bladder cancer. Am J Pathol 149: 873–882
Taubert H, Meye A and Wurl P (1996) Prognosis is correlated with p53 mutation type for soft tissue sarcoma patients. Cancer Res 56: 4134–4136
Webb DSA, Shimizu Y, van Seventer GA, Shaw S and Gerrard TL (1990) LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science 249: 1295–1297
Wiklund T, Huuhtanen R, Blomqvist C, Tukiainen E, Virolainen M, Virkkunen P, Asko-Seljavaara S, Björkenheim JM and Elomaa I (1996) The importance of a multidisciplinary group in the treatment of soft tissue sarcomas. Eur J Cancer 32A: 269–273
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Maula, S., Huuhtanen, R., Blomqvist, C. et al. The adhesion molecule CD44v6 is associated with a high risk for local recurrence in adult soft tissue sarcomas. Br J Cancer 84, 244–252 (2001). https://doi.org/10.1054/bjoc.2000.1590
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2000.1590
Keywords
This article is cited by
-
Increased CD44s and decreased CD44v6 RNA expression are associated with better survival in myxofibrosarcoma patients: a pilot study
European Journal of Medical Research (2014)
-
Expression profiling using tissue microarray in 211 malignant fibrous histiocytomas confirms the prognostic value of Ki-67
Virchows Archiv (2004)