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British Journal of Cancer (2007) 97, 971-977.
doi:10.1038/sj.bjc.6603958 www.bjcancer.com Published online 2 October 2007
Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients
N G Hurst1,2, D D Stocken1, S Wilson3, C Keh2, M J O Wakelam1,4 and T Ismail2
1Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK
2University Hospital Birmingham NHS Trust, Edgbaston, Birmingham B15 2TH, UK
3Department of Primary Care and General Practice, University of Birmingham, Birmingham B15 2TT, UK
Correspondence to: NG Hurst, Department of Surgery, Derby City General Hospital, Uttoxeter Road, Derby DE22 3NE, UK; E-mail: Nicholas.hurst@derbyhospitals.nhs.uk
4Current address: The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK
Received 25 April 2007; revised 3 August 2007; accepted 9 August 2007; published online 2 October 2007
Early detection of polyps or colorectal carcinoma can reduce colorectal carcinoma-associated deaths. Previous studies have demonstrated raised serum levels of matrix metalloproteinase 9 (sMMP-9) in a range of cancers. The aim of this study was to investigate the role of sMMP-9 levels in identifying colorectal neoplasia. Consenting patients donated a blood sample and were assessed by proforma-led history and physical examination. Samples were analysed for sMMP-9 concentration (enzyme-linked immuno-sorbant assay) and compared to final diagnoses. Logistic regression modelling determined independent factors associated with neoplasia. A total of 365 patients were recruited of whom 300 were analysed, including 46 normal controls. A total of 27 significant adenomas and 63 malignancies were identified. The median sMMP-9 concentration was 443ng ml-1 (IQR: 219-782; mean: 546). Patients with neoplasia had significantly elevated sMMP-9 levels (P<0.001). Logistic regression modelling identified elevated log(sMMP-9) as the most significant predictor of neoplasia (
2=38.33, P<0.001). Other significant factors were age, sex, smoking history, abdominal pain and weight loss. The model accurately predicted neoplasia in 77.3% of cases. Sensitivity and specificity were 77.9 and 77.1%. sMMP-9 estimation can accurately stratify patient to low- or high-risk cohorts. Serum sampling is a potential means of avoiding unnecessary colonoscopy and reducing patient anxiety, iatrogenic morbidity and mortality, and cost.Keywords: colorectal; matrix metalloproteinase; screening; risk
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