European Urology
Prostate Cancer
Expression and Prognostic Value of CD44 Standard and Variant v3 and v6 Isoforms in Prostate CancerAaltomaa S.a · Lipponen P.c · Ala-Opas M.a · Kosma V.-M.b, cDepartments of aUrology and bPathology, Kuopio University Hospital, and cDepartment of Pathology and Forensic Medicine, University of Kuopio, Finland
|
|
Log in to MyKarger to check if you already have access to this content.
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Subscribe
For eJournal Archive and eJournal Backfiles information please contact Karger service
Article / Publication Details
Published online: February 08, 2001
Issue release date: February 2001
Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 4
ISSN: 0302-2838 (Print)
eISSN: 1873-7560 (Online)
For additional information: https://www.karger.com/EUR
Abstract
Background: The adhesion molecule CD44 standard (CD44s), and its variant isoforms v3 and v6 are associated with cell–to–cell adhesion. The down–regulation of CD44 standard and its variant isoform CD44v6 is linked with early cancer cell dissemination, but the relationship between CD44v3 and malignant features of prostate cancer (PC) has not been established previously. Methods: The expression of CD44s and its CD44v3 and CD44v6 isoforms was analysed by immunohistochemistry in 209 archival PC biopsy specimens to establish their prognostic value. Results: Down–regulation of CD44s and CD44v6 was related to high T classification, metastasis, high Gleason score, DNA aneuploidy, high S–phase fraction, high mitotic index, perineural growth and dense amount of tumour infiltrating lymphocytes (p<0.03 for all). Down–regulation of CD44s and CD44v6 was related to poor survival in the entire cohort (p<0.0001), in M0 tumours (p<0.001) and in T1–2M0 tumours (p<0.05). In needle biopsies and TURP specimens, the prognostic impact of the investigated parameters was similar. In the multivariate analysis, T classification (p = 0.0009), presence of metastases (p<0.0001), Gleason score (p = 0.0060) and CD44v6 (p = 0.0220) expression were independent prognostic factors. In M0 tumours, T classification (p<0.0001) and CD44v6 (p = 0.003) independently predicted survival. Conclusion: Down–regulation of CD44s and its CD44v6 isoform is related to tumour malignancy and unfavourable prognosis in PC.
Related Articles:
References
- Aaltomaa S, Lipponen P, Vesalainen S, Ala–Opas M, Eskelinen M, Syrjänen K: Value of Ki–67 immunolabelling as a prognostic factor in prostate cancer. Eur Urol 1997;32:410–415.
- Richmond PJM, Karayiannakis AJ, Nagafuchi A, Gnatelli M: Aberrant E–cadherin and alpha–catenin expression in prostate cancer: Correlation with patient survival. Cancer Res 1997;57: 3189–3193.
- Vesalainen S, Lipponen P, Talja M, Syrjänen K: Mitotic activity and prognosis in prostatic adenocarcinoma. Prostate 1995;26:80–86.
- Gao AC, Lou W, Dong J–T, Isaacs JT: CD44 is a metastasis supressor gene for prostatic cancer located on human chromosome 11p13. Cancer Res 1997;57:846–849.
-
Zhu D, Bourguignon LY: The ankyrin–binding domain of CD44s is involved in regulating hyaluronic acid–mediated functions and prostate tumor cell transformation. Cell Motil Skeleton 1998;39:209–222.
- Bourguignon LY, Iida N, Welsh CF, Zhu D, Krongrad A, Pasquale D: Involvement of CD44 and its variant isoforms in membrane–cytoskeleton interaction, cell adhesion and tumour metastasis. J Neurooncol 1995;26:201– 208.
- Gao AC, Lou W, Sleeman JP, Isaacs JT: Metastasis supression by the standard CD44 isoform does not require the binding of prostate cancer cells to hyaluronate. Cancer Res 1998;58: 2350–2352.
- DeMarzo AM, Bradshaw C, Sasuvageot J, Epstein JI, Miller GJ: CD44 and CD44v6 down–regulation in clinical prostate carcinoma: Relation to Gleason grade and cytoarchitecture. Prostate 1998;34:162–168.
- Kallakury BV, Yang F, Smith KE, Kausik SJ, Tacy NJ, Fisher HAG, Kaufman R, Figge H, Ross JS: Decreased levels of CD44 protein and mRNA in prostate carcinoma. Correlation with tumour grade and ploidy. Cancer 1996;78: 1461–1469.
- Noordzij MA, Steenbrugge GJ, Verkaik NS, Schroder FH, van der Kwast TH: The prognostic value of CD44 isoforms in prostate cancer patients treated by radical prostatectomy. Clin Cancer Res 1997;3:805–815.
- Nagabhushan M, Pretlow TG, Guo YJ, Amini SB, Sy MS: Altered expression of CD44 in human prostate cancer during progression. Am J Clin Pathol 1996;106:647–651.
-
UICC: TNM Classification of Malignant Tumours. Geneva, UICC, 1992.
-
Gleason DF: Histologic grading and clinical staging of prostatic carcinoma; in Tannenbaum M: Urologic Pathology: The Prostate. Philadelphia, Lea & Febiger, 1977, 171–197.
-
Vesalainen S, Lipponen P, Talja M, Syrjänen K: Histological grade, perineural infiltration, tumor–infiltrating lymphocytes and apoptosis as determinants of long–term prognosis in prostatic adenocarcinoma. Eur J Cancer 1994; 30A:1797–1803.
- Vesalainen S, Nordling S, Lipponen P, Talja M, Syrjänen K: Progression and survival in prostatic adenocarcinoma: A comparison of clinical stage, Gleason grade, S–phase fraction and DNA ploidy. Br J Cancer 1994;70:309–314.
- Ropponen KM, Eskelinen MJ, Lipponen PK, Alhava E, Kosma V–M: Expression of CD44 and variant proteins in human colorectal cancer and its relevance for prognosis. Scan J Gastroenterol 1998;33:301–309.
- Lipponen P, Aaltomaa S, Kosma V–M, Ala–Opas M, Eskelinen M: Expression of CD44 standard and variant–v6 proteins in transitional cell bladder tumours and their relation to prognosis during a long term follow–up. J Pathol 1998;186:157–164.
- Lokeshwar BL, Lokeshwar VB, Block NL: Expression of CD44 in prostate cancer cells: Association with cell proliferation and invasive potential. Anticancer Res 1995;15:1191– 1198.
- Aaltomaa S, Eskelinen M, Lipponen P: Expression of cyclin A and D proteins in prostate cancer and their relation to clinicopathological variables and patient survival. Prostate 1999; 38:175–182.
-
Kallakury BV, Sheehan CE, Ambros RA, Fisher HA, Kaufman RP Jr, Ross JS: The prognostic significance of p34cdc2 and cyclin D1 protein expression in prostate adenocarcinoma. Cancer 1998;80:753–763.
External Resources
-
Kallakury BV, Sheehan CE, Rhee SJ, Fisher HA, Kaufman RP Jr, Rifkin MD, Ross JS: The prognostic significance of proliferation–associated protein p120 expression in prostate adenocarcinoma: A comparison with cyclins A and B1, Ki–67. Proliferating cell nuclear antigen, and p34cdc2. Cancer 2000;184:45–62.
-
Gunther U: Adhesion in leucocyte homing and differentiation. Curr Topics Microbiol Immunol 1993;184:45–62.
- Brewster SF, Oxley JD, Trivella M, Abbott CD, Gleason DF: Preoperative p53, bcl–2, CD44 and E–cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy. J Urol 1999;161:1238– 1243.
Article / Publication Details
Published online: February 08, 2001
Issue release date: February 2001
Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 4
ISSN: 0302-2838 (Print)
eISSN: 1873-7560 (Online)
For additional information: https://www.karger.com/EUR
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Get Permission