The histologic and proliferative characteristics of 16 colonic biopsies taken from an operative specimen of a 38-year-old female patient with multiple polyposis are presented. Kinetic measurements are based on "HTdR incorporation accomplished in vitro, using both single and double labelling techniques. Epithelial cells in adenomatous tissue were more actively engaged in DNA synthesis than those normal-appearing mucosa (L.I. 13.0 5 6.9 versus 9.3 ? 1.6); however, because of extreme variability between biopsies, the difference was not significant. No difference in S phase duration was found, but a faster turnover time (T,) than that in the normal appearing colonic mucosa was estimated (T, 52.6 hours versus 74.2 hours).
Only two of ten biopsies containing normal-appearing mucosa had a completely normal incorporation pattern with proliferative cells located only in the lower two thirds of crypts. Eight biopsies showed extension of the proliferative compartment to the luminal surface. One of these eight also expressed an additional proliferative defect, namely, a shift of the major zone of DNA synthesis to the middle and upper regions of the crypts. This specimen had been located adjacent to an area of microscopic adenoma.
Subpopulations of labelled epithelial cells showing transition from normal to hyperplastic or to adenomatous appearance were in the otherwise normal-appearing crypts. The majority of labelled hyperplastic-appearing cells occupied the lower thirds of the crypts, whereas 68% of labelled adenomatous-appearing cells were located in the middle and upper zones of the glands.
Based on these observations, the development of an adenoma is believed forecast by the redistribution of the proliferative compartment toward toward the surface. A further stage in tumorogenesis before the appearance of a focus of neoplasia is the emergence of actively proliferating cells transforming to a more adenomatous appearance primarily in that same location, that is, the middle and upper third of the colonic crypts.