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

BMJ 1994;308:619-624 (5 March)

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

Y Matsumura, D Hanbury, J Smith, D Tarin

Nuffield Department of Pathology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU Department of Urology, Churchill Hospital, Oxford OX3 8LJ Correspondence to: Dr Tarin.

Abstract

Objective : To investigate non-invasive detection of cancerby testing for unusual CD44 gene activity in a clinical sampleas an indicator of exfoliated tumour cells.
Design : Case-control study.
Subjects : 44 unselected, consecutive patients with bladdercancer and 46 people with no evidence of neoplasia.
Main outcome measure : Presence or absence of large CD44 geneproducts containing exon 6 derivatives in urine samples.
Results : Novel abnormalities in the pattern of expressionof this gene, seen specifically in tumour tissue, led to cloningof a newly recognised coding region in it (exon 6). This wastested as a probe for detection of exfoliated malignant cellsin naturally voided urine. CD44 gene products extracted fromthe urine and amplified with polymerase chain reaction containedpredicted electrophoretic band of 735 base pairs in 40 of the44 patients with bladder cancer (sensitivity 91%). Productsfrom 38 of the 46 people with no evidence of neoplasia showedno such band (specificity 83%).
Conclusions : Unusual activity of the CD44 locus in neoplasiaand malignancy is confirmed, and techniques for the analysisof such activity can enable non-invasive investigation of patientsfor primary or recurrent bladder cancer or for other tumoursthat shed neoplastic cells into body fluids.

Clinical implications

Clinical implications
Early stage bladder cancer can be effectively treated by resection, but it is often asymptomatic so that affected paients who could benefit are difficult to identify
With gene amplification techniques abnormal activity of the CD44 gene has been found in tumour tissue
In this study abnormal CD44 activity was confirmed with improved techniques in tumours from various tissues including breast, colon, and bladder
Abnormal CD44 gene activity was also found in exfoliated cells in urine samples from 91% (40/44) of patients with bladder cancer, while no such abnormality was found in samples from 83% (38/46) of non-neoplastic controls
Technical improvements to the assay should substantially increase specificity of detection, and this non-invasive technique may be suitable for early detection of primary bladder tumours and monitoring for recurrent disease

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