source: Cancer epidemiology, biomarkers & prevention
Keller J J, Offerhaus G J, Hylind L M, Giardiello F M
Innormal colorectal epithelium, apoptosis occurs at the surface and proliferation is restrictedto the lower base of the crypt. Inversion of this compartmentalization is an early event during the adenoma-carcinoma sequence.
FAP3 patients develop hundreds of adenomas and eventually colorectal carcinoma. The normal appearing colorectal mucosa of FAP patients is marked by altered cell kinetics with disturbance of the localization of proliferation and apoptosis. Sulindac causes regression of adenomas in FAP patients, presumably through induction of apoptosis. We reported previously that sulindac decreases the ratio between apoptosis at the crypt base and at the surface apoptotic ratio (AR) in the normal rectal mucosa of FAP patients with adenoma regression on sulindac. One patient without reversal of the AR developed a “breakthrough carcinoma” during sulindac therapy, suggesting a potential role for this parameter as biomarker.
The hypothesis tested in the present study was that the change in AR is useful as an intermediate biomarker for response to sulindac treatment and adenoma development in presymptomatic FAP patients enrolled in a primary chemoprevention trial.
Academic Medical Center
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