Quantification of proliferative activity in colorectal adenomas by mitotic counts: relationship to degree of dysplasia and histological type.

Abstract

Aim-Proliferative activity of tumours reflects their malignant potential. In colorectal adenomas, a subjective impression of the number of mitoses is a criterion often used to assess the degree ofdysplasia. Since these subjective impressions of mitotic activity may lack reproducibility, the aim of this study was to perform an objective analysis. Methods-Mitotic counts were conducted in tissue sections of 59 colorectal adenomas. Ofthese, 20 showed mild, 20 moderate, and 19 severe dysplasia, according to blind duplicate assessments by two pathologists. Forty three were classified as tubular adenomas and 16 as "villous" adenomas (tubulo-villous and villous). The number ofmitoses, both per unit area of epithelium (area weighted mitotic counts, AWMC) and per colonic crypt (mitotic counts per colonic crypt MCCC), was scored in the most dysplastic area within the adenoma. Mitotic figures were counted using a light microscope (ocular x 10, objective x 40, NA 0 75), and the area of the glandular epithelium was measured using an interactive video overlay measurement system. Twenty glands per specimen were assessed. In the intra-observer reproducibility tests, the coefficients of error for the AWMC and MCCC were 4 5% and 7-4%/o respectively.Results-For the AWMC a significant difference was found between mild and moderate as well as between mild and severe dysplasia, but not between moderate and severe dysplasia. The results of the MCCC showed the same trend, but the differences did not reach a significant level. Furthermore, cases classified as mild dysplasia were found that showed numerous mitoses, while cases classified as severe dysplasia were found with only very few mitoses. No significant difference in AWMC was found between tubular and villous adenomas. Thus the different malignant potential of tubular and villous adenomas was not reflected by a difference in AWMC. A seemingly strong difference for MCCC between tubular and "villous" adenomas appeared to depend completely on the difference in crypt size between these two groups. Conclusions-The area weighted mitotic count, rather than the mitotic count per colonic crypt, may be useful for assessing the proliferation rate in colorectal adenomas. (J Clin Pathol 1995;48:620-625)

The value of phosphohistone H3 as a proliferation marker for evaluating invasive breast cancers: A comparative study with Ki67

“…However, M grade counted by PHH3 did not always match with the M grade counted on H&E (MAI). A possible explanation for the discrepancy is the subjectivity associated with mitotic activity index and inaccurate localizations of mitotically active areas [ 28 – 30 ]. On a similar note, studies noting superior survival correlations of Ki67 compared to mitotic index may be explained by possible masked, unidentified mitosis which may have underestimated the actual proliferative potential of mitotic index [ 31 , 32 ].…”

Interaction of Calcium Supplementation and Nonsteroidal Anti-inflammatory Drugs and the Risk of Colorectal Adenomas

“…However, the mechanisms underlying these findings remain unknown. Experimental studies regarding cellular growth and apoptosis have not consistently reported differences between early adenomas and advanced adenomas (59)(60)(61)(62)(63)(64)(65). There are suggestions that advanced adenomas have more genetic changes than the earlier lesions, but differences in the expression and mutation status of p53, bcl-2, K-ras, and others have also been inconsistent (66)(67)(68).…”

Clinical decision making in Barrett's oesophagus can be supported by computerized immunoquantitation and morphometry of features associated with proliferation and differentiation

“…It is well known that in dysplastic BO, like in other premalignant lesions in the gastrointestinal tract, the aberrant proliferation is characterized by the two following features. [28][29][30] Firstly, there is an increase in the proliferative activity; secondly, this increased proliferation is accompanied by an upward shift of DNA-synthesizing cells from the progenitor zone in the deep part of the crypts towards the luminal surface. As a consequence, cells maintain an undifferentiated phenotype in which there is an increased nuclear-cytoplasmic ratio with hyperchromatism.…”