Non-invasive detection of colorectal tumours by the combined application of molecular diagnosis and the faecal occult blood test

Technische Universität Dortmund, Dortmund, North Rhine-Westphalia, Germany
Cancer Letters (Impact Factor: 5.62). 12/2005; 229(1):33-41. DOI: 10.1016/j.canlet.2004.12.011
Source: PubMed


The treatment of early-stage tumours decreases the overall mortality of colorectal tumour patients. In this retrospective study we determined the sensitivity and the specificity of the faecal occult blood test (FOBT) and the molecular diagnosis (MD). We analysed 57 stool samples from patients with colorectal carcinomas for the presence of occult blood using a standard FOBT and for alterations in the three different tumour relevant markers APC, BAT26 and L-DNA. Stool samples from 44 control donors were analysed to determine the specificity of the applied methods. Twenty-nine (51%; 95% confidence interval (CI): 38-63%) stool samples of the cancer patients gave positive FOBT results. Thirty-seven (65%; CI: 52-76%) samples showed alterations in at least one DNA marker. Sixteen (28%) samples were positive only in the FOBT, and 24 (42%) samples showed a positive result exclusively in MD. The combined application of both methods resulted in a sensitivity of 93% (CI: 83-97%) and an overall specificity of 89% (CI: 76-95%). The combined application of FOBT and MD resulted in an overall sensitivity, which could not be achieved by any of the methods alone and which is in the range of invasive diagnostic methods.

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    • "(vi) APC, BAT-26, and L-DNA [83] "
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    ABSTRACT: Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.
    Full-text · Article · Sep 2012 · Gastroenterology Research and Practice
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    • "b Specificity is based on controls including polyps. Ahlquist et al, 2000 21 Tagore et al, 2003 22 Calistri et al, 2003 23 Leung et al, 2004 48 Whitney et al, 2004 26 Imperiale et al, 2004 27 Petko et al, 2005 49 Kutzner et al, 2005 168 Matsushita et al, 2005 169 Itzkowitz et al, 2007 29 Abbaszadegan et al, 2007 179 "
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    ABSTRACT: Detecting and removing high-risk adenomas and early colorectal cancer (CRC) can reduce mortality of this disease. The noninvasive fecal occult blood test (FOBT; guaiac-based or immunochemical) is widely used in screening programs and although effective, it leaves room for improvement in terms of test accuracy. Molecular tests are expected to be more sensitive, specific and informative than current detection tests, and are promising future tools for CRC screening. This review provides an overview of the performances of DNA, RNA, and protein markers for CRC detection in stool and blood. Most emphasis currently is on DNA and protein markers. Among DNA markers there is trend to move away from mutation markers in favor of methylation markers. The recent boost in proteomics research leads to many new candidate protein markers. Usually in small series, some markers show better performance than the present FOBT. Evaluation in large well-controlled randomized trials is the next step needed to take molecular markers for CRC screening to the next level and warrant implementation in a screening setting.
    Full-text · Article · Mar 2011 · Clinical Colorectal Cancer
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    ABSTRACT: Eine Reduktion der Sterblichkeit durch Darmkrebs scheitert bisher an der Unvereinbarkeit von Zuverlässigkeit einerseits und geringer Patientenbelastung und logistischem Aufwand andererseits. Existierende molekulare Diagnoseverfahren können derzeit nur in wissenschaftlichen Laboren durchgeführt werden. Für genetische Instabilität auf chromosomaler (CIS) und auf Nukleotid-Ebene wurden daher in der vorliegenden Arbeit Strategien getestet um existierende molekulare Methoden in im klinischen Umfeld etablierte Formate zu übertragen. Im Fall von durch APC-Mutation bedingter CIS stellen strukturelle Unordnung und Instabilität des Proteinprodukts die Hürde dar. Für Microsatelliten-Instabilität ist die Tatsache, dass die für Darmkrebs charakteristischste Sequenz ein polyA-Mononucleotid-Repeat ist ein Ausschlussfaktor für viele Ausleseverfahren, da natürliche Schwankungen zu falsch-positiven Ergebnissen führen. Direktes Auslesen der Länge durch Sonden scheitert an schwachen A:T-Wechselwirkungen.
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