Detection of stool DNA mutations before and after treatment of colorectal neoplasia.
BACKGROUND
Whether stool DNA abnormalities arise solely from colorectal neoplastic lesions or are due to more pervasive field effects is not known. In the current study, the authors conducted a prospective multicenter study to evaluate the performance of stool-based DNA testing in a large cohort and to examine whether the findings before treatment persist after surgical resection and/or adjuvant therapy.


METHODS
Patients with newly diagnosed colorectal carcinoma or advanced adenomas (AA) provided stool samples before therapy, 1-3 months after surgical resection, and 6-9 months postresection. Stool samples were analyzed using the multi-target DNA assay panel (MTAP) consisting of 23 markers: 21 mutations in the p53, K-ras, and APC genes, a microsatellite instability marker (BAT-26), and the DNA integrity assay (DIA), a marker of loss of apoptosis.


RESULTS
Overall, 49 of 91 individuals (54%) tested positive with the MTAP test. The sensitivity of the MTAP test was 63% for invasive tumors compared with 26% for AA. Individuals whose lesions had a more advanced TNM stage or were located distal to the splenic flexure were significantly more likely to have a positive MTAP test. Of the 79 samples collected at 1-3 months after surgical resection of the neoplasm, 14 (18%) had a positive MTAP result, 12 of which were positive for DIA only. Of those collected at 6-9 months of follow-up, 5 of 72 (7%) tested positive on the MTAP panel.


CONCLUSIONS
Although many samples collected 1-3 months after surgical resection of the colorectal neoplasm tested positive on the MTAP, most were negative by 6-9 months, indicating that stool DNA abnormalities disappear after treatment of the neoplastic lesions. Surgery and chemoradiation appear to induce transient DIA abnormalities that may be independent of the presence of neoplasia.
Syngal
Sapna
S
Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. ssyngal@partners.org
Stoffel
Elena
E
Chung
Daniel
D
Willett
Christopher
C
Schoetz
David
D
Schroy
Paul
P
Jagadeesh
Deepa
D
Morel
Kathleen
K
Ross
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D004273:DNA, Neoplasm / Q000032:analysis*; D005243:Feces / Q000737:chemistry*; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm