Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT).
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 s...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3896420?pdf=render |
| _version_ | 1819138777253150720 |
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| author | Russell I Heigh Tracy C Yab William R Taylor Fareeda T N Hussain Thomas C Smyrk Douglas W Mahoney Michael J Domanico Barry M Berger Graham P Lidgard David A Ahlquist |
| author_facet | Russell I Heigh Tracy C Yab William R Taylor Fareeda T N Hussain Thomas C Smyrk Douglas W Mahoney Michael J Domanico Barry M Berger Graham P Lidgard David A Ahlquist |
| author_sort | Russell I Heigh |
| collection | DOAJ |
| description | 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).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).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).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. |
| first_indexed | 2024-12-22T11:12:09Z |
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| spelling | doaj.art-b2df20b3bbd2472cac0ea80c877986622022-12-21T18:28:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8565910.1371/journal.pone.0085659Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT).Russell I HeighTracy C YabWilliam R TaylorFareeda T N HussainThomas C SmyrkDouglas W MahoneyMichael J DomanicoBarry M BergerGraham P LidgardDavid A AhlquistPrecursors 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).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).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).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.http://europepmc.org/articles/PMC3896420?pdf=render |
| spellingShingle | Russell I Heigh Tracy C Yab William R Taylor Fareeda T N Hussain Thomas C Smyrk Douglas W Mahoney Michael J Domanico Barry M Berger Graham P Lidgard David A Ahlquist Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT). PLoS ONE |
| title | Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT). |
| title_full | Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT). |
| title_fullStr | Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT). |
| title_full_unstemmed | Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT). |
| title_short | Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT). |
| title_sort | detection of colorectal serrated polyps by stool dna testing comparison with fecal immunochemical testing for occult blood fit |
| url | http://europepmc.org/articles/PMC3896420?pdf=render |
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