Fecal DNA Test Accurately Diagnoses Colorectal Neoplasia

The sensitivities of a multimarker test for stool DNA (sDNA) and a plasma test for methylated Septin 9 (SEPT9) have been compared in identifying patients with large adenomas or CRC.

Scientists at the Mayo Clinic (Rochester, MN, USA) analyzed paired stool and plasma samples from 30 patients with CRC and 22 with large adenomas from the clinic's archives. Control included 46 fecal and 49 plasma samples from age- and sex-matched patients with normal colonoscopy results. The sDNA test is an assay for four methylated genes; a mutant form of the Kirsten rat sarcoma viral oncogene (KRAS); the β-actin gene, and measures hemoglobin levels by the porphyrin method.

The sDNA assay was performed at Exact Sciences Laboratories (Madison, WI, USA) and the plasma test, the methylated DNA detection by real-time polymerase chain reaction (PCR) for Septin 9 (SEPT9) was performed at the ARUP Laboratories (Salt Lake City, UT, USA). Results were considered positive, based on the manufacturer's specificity cutoff values of 90% and 89%, respectively.

The sDNA test detected 82% of precancerous polyps compared to only 14% percent detected by SEPT9. The sDNA test identified 87% of cancers at any stage, compared to 60% with SEPT9. The sDNA was even more effective at detecting curable-stage cancer, that is stages I, II or III, and detecting such cases 91% of the time, compared to just 50% with SEPT9. The SEPT9's rate of false-positives was 27%, which is nearly four times that of stool DNA at 7%. The authors concluded that based on analyses of paired samples, the sDNA test detects nonmetastatic CRC and large adenomas with significantly greater levels of sensitivity than the SEPT9 test. These findings might be used to modify approaches for CRC prevention and early detection assays.

David A Ahlquist , MD, the senior author of the study, said "It was important to compare tests head-to-head. Our findings are clear and entirely consistent with the biology of the marker release. Cancerous and precancer cells are shed into the stool and detected by the stool DNA test long before tumors progress to invade the bloodstream for later detection by the plasma SEPT9 screening test.” The study is slated for publication in the March 2012 issue of the journal Clinical Gastroenterology and Hepatology.

Related Links:
Mayo Clinic
Exact Sciences Laboratories
ARUP Laboratories