QUANTITATIVE ASSESSMENT OF NORMAL AND POTENTIALLY PREMALIGNANT EPITHELIUM AT DIFFERENT LEVELS OF HUMAN COLORECTAL CRYPTS

The present study uses morphometric techniques to assess whether alter ed differentiation patterns exist in PPM which might reflect its prema lignant status. Samples were obtained from resected malignant lesions of large bowels of 10 Chinese patients. Normal (N) samples were biopsi ed from the margins of each resected large bowel. Potentially premalig nant (PPM) mucosae were obtained from within 2 cm of the margins of th e malignant lesions. Tissues were processed for histological examinati on and using strict criteria, colorectal crypts were divided into basa l (B), intermediate (I) and surface (S) segments. Interactive digitisa tion of sections from each group was used to generate the following mo rphometric parameters in each segment: nuclear profile circularity ind ices (NSF and NCI); nuclear numerical density (N-A and N-V); the degre e of deviation of the major nuclear axis in relation to the epithelial -connective junction (AGDMAX); cell height (CH); the distance between nuclear apex to cell apex (DNACA); the distance between cell base to n uclear apex (DCBNA); stratification index (SI) - the ratio of DCBNA an d CH; and the volume density of mucous vacuoles in the reference epith elium ((VMV)-V-V,EP) In comparisons of different segments within group s, the nuclei at the S segment of N and PPM crypts were more irregular and less circular in shape than nuclei from other segments. There was a shift of nuclear profile shape (NSF and NCI) from circular to ellip siodal between B and S segments. In comparisons of similar segments be tween groups, no significant nuclear shape changes were detected in nu clei of PPM crypts when compared with nuclei in similar segments of N crypts and the pattern of nuclear shape alterations resembled those of normal crypts. In comparisons of different segments within groups of N and PPM crypts, AGDMAX. DNACA, DCBNA, CH and SI parameters demonstra ted that epithelial cells at the I segments have more centrally positi oned nuclei with the tallest epithelial height when compared with epit helial cells in other segments of both crypts. In B segments, nuclear N-A and N-V were almost double those of other segments in both N and P PM crypts, with marked reductions in these parameters between B and I segments. V-VMV,V-EP was significantly highest in the I segment and si gnificantly lowest in the S segment of both groups. Both N and PPM cry pts showed similar trends in V-VMV,V-EP within the crypt segments but when comparing similar segments between both crypts, a significant dif ference was detected only between S segments. The alterations of nucle ar shape and packing densities, orientation and mucous content in N cr ypts were similarly expressed in PPM crypts and distinct differences i n numerical density (N-V) and stratification index existed in crypts b etween these two groups when comparing similar segments. All values in PPM were consistently lower when compared with N crypts. These prelim inary observations may represent a subtly altered state of cellular di fferentiation in PPM which may be a reflection of early preneoplastic transformation.