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. 1994 Mar 5;308(6929):619–624. doi: 10.1136/bmj.308.6929.619

Non-invasive detection of malignancy by identification of unusual CD44 gene activity in exfoliated cancer cells.

Y Matsumura 1, D Hanbury 1, J Smith 1, D Tarin 1
PMCID: PMC2539711  PMID: 8148709

Abstract

OBJECTIVE--To investigate non-invasive detection of cancer by testing for unusual CD44 gene activity in a clinical sample as an indicator of exfoliated tumour cells. DESIGN--Case-control study. SUBJECTS--44 unselected, consecutive patients with bladder cancer and 46 people with no evidence of neoplasia. MAIN OUTCOME MEASURE--Presence or absence of large CD44 gene products containing exon 6 derivatives in urine samples. RESULTS--Novel abnormalities in the pattern of expression of this gene, seen specifically in tumour tissue, led to cloning of a newly recognised coding region in it (exon 6). This was tested as a probe for detection of exfoliated malignant cells in naturally voided urine. CD44 gene products extracted from the urine and amplified with polymerase chain reaction contained predicted electrophoretic band of 735 base pairs in 40 of the 44 patients with bladder cancer (sensitivity 91%). Products from 38 of the 46 people with no evidence of neoplasia showed no such band (specificity 83%). CONCLUSIONS--Unusual activity of the CD44 locus in neoplasia and malignancy is confirmed, and techniques for the analysis of such activity can enable non-invasive investigation of patients for primary or recurrent bladder cancer or for other tumours that shed neoplastic cells into body fluids.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Britton J. P., Dowell A. C., Whelan P., Harris C. M. A community study of bladder cancer screening by the detection of occult urinary bleeding. J Urol. 1992 Sep;148(3):788–790. doi: 10.1016/s0022-5347(17)36720-4. [DOI] [PubMed] [Google Scholar]
  2. Dougherty G. J., Landorp P. M., Cooper D. L., Humphries R. K. Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells. J Exp Med. 1991 Jul 1;174(1):1–5. doi: 10.1084/jem.174.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hedin A., Carlsson L., Berglund A., Hammarström S. A monoclonal antibody-enzyme immunoassay for serum carcinoembryonic antigen with increased specificity for carcinomas. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3470–3474. doi: 10.1073/pnas.80.11.3470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Heider K. H., Dämmrich J., Skroch-Angel P., Müller-Hermelink H. K., Vollmers H. P., Herrlich P., Ponta H. Differential expression of CD44 splice variants in intestinal- and diffuse-type human gastric carcinomas and normal gastric mucosa. Cancer Res. 1993 Sep 15;53(18):4197–4203. [PubMed] [Google Scholar]
  5. Heider K. H., Hofmann M., Hors E., van den Berg F., Ponta H., Herrlich P., Pals S. T. A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps. J Cell Biol. 1993 Jan;120(1):227–233. doi: 10.1083/jcb.120.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Higgins G. A., Jr, Amadeo J. H., McElhinney J., McCaughan J. J., Keehn R. J. Efficacy of prolonged intermittent therapy with combined 5-fluorouracil and methyl-CCNU following resection for carcinoma of the large bowel. A Veterans Administration Surgical Oncology Group report. Cancer. 1984 Jan 1;53(1):1–8. doi: 10.1002/1097-0142(19840101)53:1<1::aid-cncr2820530102>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  7. Jackson D. G., Buckley J., Bell J. I. Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain. J Biol Chem. 1992 Mar 5;267(7):4732–4739. [PubMed] [Google Scholar]
  8. Kantoff P. W. Bladder cancer. Curr Probl Cancer. 1990 Sep-Oct;14(5):233–292. doi: 10.1016/0147-0272(90)90016-j. [DOI] [PubMed] [Google Scholar]
  9. Koss L. G., Deitch D., Ramanathan R., Sherman A. B. Diagnostic value of cytology of voided urine. Acta Cytol. 1985 Sep-Oct;29(5):810–816. [PubMed] [Google Scholar]
  10. Matsumura Y., Tarin D. Significance of CD44 gene products for cancer diagnosis and disease evaluation. Lancet. 1992 Oct 31;340(8827):1053–1058. doi: 10.1016/0140-6736(92)93077-z. [DOI] [PubMed] [Google Scholar]
  11. Matzkin H., Moinuddin S. M., Soloway M. S. Value of urine cytology versus bladder washing in bladder cancer. Urology. 1992 Mar;39(3):201–203. doi: 10.1016/0090-4295(92)90288-8. [DOI] [PubMed] [Google Scholar]
  12. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Screaton G. R., Bell M. V., Jackson D. G., Cornelis F. B., Gerth U., Bell J. I. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160–12164. doi: 10.1073/pnas.89.24.12160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sidransky D., Von Eschenbach A., Tsai Y. C., Jones P., Summerhayes I., Marshall F., Paul M., Green P., Hamilton S. R., Frost P. Identification of p53 gene mutations in bladder cancers and urine samples. Science. 1991 May 3;252(5006):706–709. doi: 10.1126/science.2024123. [DOI] [PubMed] [Google Scholar]
  15. Tanabe K. K., Ellis L. M., Saya H. Expression of CD44R1 adhesion molecule in colon carcinomas and metastases. Lancet. 1993 Mar 20;341(8847):725–726. doi: 10.1016/0140-6736(93)90490-8. [DOI] [PubMed] [Google Scholar]
  16. Tarin D., Matsumura Y. Deranged CD44 gene activity in malignancy. J Pathol. 1993 Dec;171(4):249–250. doi: 10.1002/path.1711710402. [DOI] [PubMed] [Google Scholar]
  17. Tarin D., Price J. E. Influence of microenvironment and vascular anatomy on "metastatic" colonization potential of mammary tumors. Cancer Res. 1981 Sep;41(9 Pt 1):3604–3609. [PubMed] [Google Scholar]
  18. Wielenga V. J., Heider K. H., Offerhaus G. J., Adolf G. R., van den Berg F. M., Ponta H., Herrlich P., Pals S. T. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993 Oct 15;53(20):4754–4756. [PubMed] [Google Scholar]
  19. Winawer S. J., Schottenfeld D., Flehinger B. J. Colorectal cancer screening. J Natl Cancer Inst. 1991 Feb 20;83(4):243–253. doi: 10.1093/jnci/83.4.243. [DOI] [PubMed] [Google Scholar]

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