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

Kutzner, Nadine; Hoffmann, Ingrid; Linke, Christina; Thienel, Thomas; Grzegorczyk, Marco; Urfer, Wolfgang; Martin, Dirk; Winde, Günther; Traska, T; Hohlbach, G.; Müller, Klaus‐Michael; Kühnen, C.; Müller, Oliver

doi:10.1016/j.canlet.2004.12.011

Cited by 21 publications

(16 citation statements)

References 15 publications

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“…Still, the results obtained show the power of combining FIT with a DNA methylation marker. This is in line with recent findings that showed an improved test performance of combining other molecular markers (i.e., APC, BAT26, and long-DNA) with FOBT (12,38).…”

Section: Discussionsupporting

confidence: 80%

“…This test performance though, still leaves room for improvement which could come from molecular stool tests like those testing for tumor DNA in stool. Multiple assays have been developed and evaluated for this purpose, but sensitivities still remain suboptimal (8)(9)(10)(11)(12)(13)(14). The recently introduced combination of mutation markers with DNA methylation markers has yielded substantially improved test performance (13,15,16).…”

Section: Introductionmentioning

confidence: 99%

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DNA Methylation of Phosphatase and Actin Regulator 3 Detects Colorectal Cancer in Stool and Complements FIT

Bosch

Oort²,

Neerincx³

et al. 2012

Cancer Prevention Research

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Using a bioinformatics-based strategy, we set out to identify hypermethylated genes that could serve as biomarkers for early detection of colorectal cancer (CRC) in stool. In addition, the complementary value to a Fecal Immunochemical Test (FIT) was evaluated. Candidate genes were selected by applying cluster alignment and computational analysis of promoter regions to microarray-expression data of colorectal adenomas and carcinomas. DNA methylation was measured by quantitative methylation-specific PCR on 34 normal colon mucosa, 71 advanced adenoma, and 64 CRC tissues. The performance as biomarker was tested in whole stool samples from in total 193 subjects, including 19 with advanced adenoma and 66 with CRC. For a large proportion of these series, methylation data for GATA4 and OSMR were available for comparison. The complementary value to FIT was measured in stool subsamples from 92 subjects including 44 with advanced adenoma or CRC. Phosphatase and Actin Regulator 3 (PHACTR3) was identified as a novel hypermethylated gene showing more than 70-fold increased DNA methylation levels in advanced neoplasia compared with normal colon mucosa. In a stool training set, PHACTR3 methylation showed a sensitivity of 55% (95% CI: 33-75) for CRC and a specificity of 95% (95% CI: 87-98). In a stool validation set, sensitivity reached 66% (95% CI: 50-79) for CRC and 32% (95% CI: 14-57) for advanced adenomas at a specificity of 100% (95% CI: 86-100). Adding PHACTR3 methylation to FIT increased sensitivity for CRC up to 15%. PHACTR3 is a new hypermethylated gene in CRC with a good performance in stool DNA testing and has complementary value to FIT. Cancer Prev Res; 5(3); 464-72. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

DNA Methylation of Phosphatase and Actin Regulator 3 Detects Colorectal Cancer in Stool and Complements FIT

Bosch

Oort²,

Neerincx³

et al. 2012

Cancer Prevention Research

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“…86 The other was a diagnostic case-control study in which 57 people with a diagnosis of cancer and 44 volunteer controls underwent a guaiac FOBT; sensitivity was 51% and specificity 98%. 87 These results are comparable with those of other studies of similar design included in the review, and do not alter the conclusions.…”

Section: Addendumsupporting

confidence: 85%

Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review

Soares‐Weiser²,

et al. 2007

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Objective To determine the accuracy of guaiac and immunochemical faecal occult blood tests (FOBTs) for the detection of colorectal cancer in an average-risk screening population. Methods Fifteen electronic databases, the internet, key journals and reference lists of included studies were searched. We included diagnostic accuracy studies that compared guaiac or immunochemical FOBTs with any reference standard, for the detection of colorectal cancer in an average-risk adult population, with sufficient data to construct a 2 Â 2 table.Results Fifty-nine studies were included. Thirty-three evaluated guaiac FOBTs, 35 immunochemical FOBTs and one evaluated sequential FOBTs. Sensitivities for the detection of all neoplasms ranged from 6.2% (specificity 98.0%) to 83.3% (specificity 98.4%) for guaiac FOBTs, and 5.4% (specificity 98.5%) to 62.6% (specificity 94.3%) for immunochemical FOBTs. Specificity ranged from 65.0% (sensitivity 44.1%) to 99.0% (sensitivity 19.3%) for guaiac FOBTs, and 89.4% (sensitivity 30.3%) to 98.5% (sensitivity 5.4%) for immunochemical FOBTs. Diagnostic case-control studies generally reported higher sensitivities. Sensitivities were higher for the detection of CRC, and lower for adenomas, in both the diagnostic cohort and diagnostic case-control studies for both guaiac and immunochemical FOBTs. Conclusions Immudia HemSp appeared to be the most accurate immunochemical FOBT, however, there was no clear evidence to suggest whether guaiac or immunochemical FOBTs performed better, either from direct or indirect comparisons. Poor reporting of data limited the scope of this review, and the use the Standards for Reporting of Diagnostic Accuracy guidelines is recommended for reporting future diagnostic accuracy studies.

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“…In a recent retrospective analysis of stool samples from patients with CRC and donor controls, combined results from a standard gFOBT and a panel of DNA markers (APC, BAT-26, and L-DNA) resulted in a combined sensitivity for cancer of 93% and specificity of 89%. 76 sDNA-Conclusions and Recommendations. In previous assessments of the performance of sDNA, both the ACS and the USMSTF concluded that data were insufficient to recommend screening with sDNA for average-risk individuals.…”

Section: Fitmentioning

confidence: 99%

Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology

Levin

Lieberman

McFarland

et al. 2008

CA: A Cancer Journal for Clinicians

1,560

916

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In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a screening test that primarily is effective at early cancer detection. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening. (CA Cancer J Clin 2008;58:130-160.)

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

Cited by 21 publications

References 15 publications

DNA Methylation of Phosphatase and Actin Regulator 3 Detects Colorectal Cancer in Stool and Complements FIT

DNA Methylation of Phosphatase and Actin Regulator 3 Detects Colorectal Cancer in Stool and Complements FIT

Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review

Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology

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