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Cited by 75Colorectal Cancer Screening and DetectionGenetic factors in colorectal cancerGastrointestinal Bleeding Diagnosis and Treatment

Detection of Colorectal Serrated Polyps by Stool DNA Testing: Comparison with Fecal Immunochemical Testing for Occult Blood (FIT)

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Heigh, Russell I., Yab, Tracy C., Taylor, William R., Hussain, Fareeda T. N., Smyrk, Thomas C., Mahoney, Douglas W., Domanico, Michael J., Berger, Barry M., Lidgard, Graham P., Ahlquist, David A.·2014·PLoS ONE
DOI 10.1371/journal.pone.0085659PMC PMC3896420
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Abstract

OBJECTIVES: Precursors to 1/3 of colorectal cancer (CRC), serrated polyps have been under-detected by screening due to their inconspicuous, non-hemorrhagic, and proximal nature. A new multi-target stool DNA test (multi-target sDNA) shows high sensitivity for both CRC and advanced adenomas. Screen detection of serrated polyps by this approach requires further validation. We sought to assess and compare noninvasive detection of sessile serrated polyps (SSP) ≥ 1 cm by sDNA and an occult blood fecal immunochemical test (FIT). METHODS: In a blinded prospective study, a single stool sample used for both tests was collected from 456 asymptomatic adults prior to screening or surveillance colonoscopy (criterion standard). All 29 patients with SSP ≥ 1 cm were included as cases and all 232 with no neoplastic findings as controls. Buffered stool samples were processed and frozen on receipt; Exact Sciences performed sDNA in batches using optimized analytical methods. The sDNA multi-marker panel targets methylated BMP3 (mBMP3) and NDRG4, mutant KRAS, β-actin, and hemoglobin. FIT (Polymedco OC-FIT Check) was performed in separate lab ≤ 2 days post defecation and evaluated at cutoffs of 50 (FIT-50) and 100 ng/ml (FIT-100). RESULTS: MEDIAN AGES: cases 61 (range 57-77), controls 62 (52-70), p = NS. Women comprised 59% and 51%, p = NS, respectively. SSP median size was 1.2 cm (1-3 cm), 93% were proximal, and 64% had synchronous diminutive polyps. Among multi-target sDNA markers, mBMP3 proved highly discriminant for detection of SSP ≥ 1 cm (AUC = 0.87, p<0.00001); other DNA markers provided no incremental sensitivity. Hemoglobin alone showed no discrimination (AUC = 0.50, p = NS). At matched specificities, detection of SSP ≥ 1 cm by stool mBMP3 was significantly greater than by FIT-50 (66% vs 10%, p = 0.0003) or FIT-100 (63% vs 0%, p<0.0001). CONCLUSIONS: In a screening and surveillance setting, SSP ≥ 1 cm can be detected noninvasively by stool assay of exfoliated DNA markers, especially mBMP3. FIT appears to have no value in SSP detection.

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  • Combining FIT with molecular stool markers compensates for intermittency or absence of bleeding from colorectal neoplasms while exploiting complementary value of FIT.

    “Such a combination compensates for the intermittency or absence of bleeding from colorectal neoplasms [12, 13], while exploiting the complementary value of FIT.”

    From Novel Approach to Fecal Occult Blood Testing by Assay of Erythrocyte-Specific microRNA Markers (2017) · cites this paper as [13]

    The Discussion (page unavailable) reports that sessile serrated polyps may not bleed but can shed detectable DNA into stool, supporting the rationale for molecular markers when bleeding is absent. The paper does not establish intermittent bleeding across colorectal neoplasms or show a complementary detection benefit from FIT; its findings concern sessile serrated polyps, for which FIT essentially failed to detect lesions. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Observed detection rates for advanced precancers were lower than those reported for FIT with advanced conventional adenomas and similar to those reported with SSAs.

    “observed detection rates for these advanced precancers were lower than those reported for FIT with advanced conventional adenomas [9, 11, 26] and similar to those reported with SSAs [9, 11, 13].”

    From Novel Approach to Fecal Occult Blood Testing by Assay of Erythrocyte-Specific microRNA Markers (2017) · cites this paper as [13]

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Cited by

Sorted by citations

Authors
Heigh, R. I., Yab, T. C., Taylor, W. R., Hussain, F. T. N., Smyrk, T. C., Mahoney, D. W., Domanico, M. J., Berger, B. M., Lidgard, G. P., & Ahlquist, D. A.
Affiliations
  • Mayo Clinic in Arizona (US)
  • Mayo Clinic (US)
  • Exact Sciences (United States) (US)
Corresponding author
Heigh, Russell I.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-01-20
Volume
9
Issue
1
Pages
e85659
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0085659
PMC
PMC3896420
OpenAlex
W2008724307
Cited by
75
References
0
Citations by year
2026: 3 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 11 · 2019: 6 · 2018: 8 · 2017: 13 · 2016: 7 · 2015: 11 · 2014: 2
FWCI
5.41
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Cancer Institute (P30CA015083)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK084567)
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
Keywords
serrated polyps, sessile serrated polyps, multi-target stool DNA test, fecal immunochemical test, occult blood detection, colorectal cancer screening, NDRG4, KRAS mutation, hemoglobin, polyp detection sensitivity, colorectal cancer surveillance, non-invasive detection
MeSH terms
Aged, Colonic Polyps, DNA, Feces, Female, Humans, Male, Mass Screening, Middle Aged, Occult Blood, Prospective Studies, Sensitivity and Specificity

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