Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps

• Published in: Digestive diseases and sciences Vol. 64; no. 9; pp. 2555 - 2562
• Main Authors: Cock, Charles, Anwar, Shahzaib, Byrne, Susan E., Meng, Rosie, Pedersen, Susanne, Fraser, Robert J. L., Young, Graeme P., Symonds, Erin L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2019; Springer; Springer Nature B.V
• Subjects: Adenoma - blood; Adenoma - diagnosis; Adenoma - pathology; Adult; Aged; Aged, 80 and over; Analysis; Biochemistry; Biomarkers, Tumor - blood; Blood; Blood tests; Cancer; Colonic Neoplasms - blood; Colonic Neoplasms - diagnosis; Colonic Neoplasms - pathology; Colonic Polyps - blood; Colonic Polyps - diagnosis; Colonic Polyps - pathology; Colonoscopy; Colorectal cancer; DNA; DNA Methylation; Early Detection of Cancer - methods; Epigenetic inheritance; Feces; Female; Gastroenterology; Health aspects; Hemoglobin; Hemoglobins - analysis; Hepatology; Humans; Ikaros Transcription Factor - blood; Ikaros Transcription Factor - genetics; Immunochemistry; Male; Medical examination; Medical screening; Medicine; Medicine & Public Health; Middle Aged; Mortality; Occult Blood; Oncology; Oncology, Experimental; Original Article; Pathology; Prospective Studies; Sensitivity and Specificity; Transaminases - blood; Transaminases - genetics; Transplant Surgery; Tumors; Biomarkers; Screening; Colorectal neoplasms; Occult blood; IKZF1; BCAT1
• ISSN: 0163-2116; 1573-2568; 1573-2568
• DOI: 10.1007/s10620-019-05569-8

Background Early detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there are limited studies on whether current screening techniques detect this pathology. Aims To investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP. Methods A prospective study offered FIT and a blood test (Colvera for methylated BCAT1 and IKZF1 ) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20 μg hemoglobin (Hb)/g feces. Results One thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated BCAT1/IKZF1 . The sensitivity of FIT (20 μg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%, p  < 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10 μg Hb/g feces (20.4%, p  > 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT. Conclusions Both FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.