Chromosome number distribution and cellular DNA content in colorectal adenomas from polyposis and nonpolyposis patients

Abstract

Ploidy analyses of colorectal adenomas were performed by combined flow cytometric DNA analysis of unfixed isolated nuclei and direct chromosome preparation after Colcemid incubation for 9–20 hours. Ten of 18 adenomas from nonpolyposis patients and 4 of 13 adenomas from patients with familial adenomatous polyposis yielded a mean of 25 countable metaphases (range 7–44) per tumor. Of 343 metaphases, only 38% had 46 chromosomes, and 62% were nondiploid. All but one adenoma had diploid or peridiploid modes in the range of 46–50 chromosomes. One adenoma was hyperploid, with a mode of 74 chromosomes and a correspondingly increased nuclear DNA content. In another two adenomas, the DNA analyses showed small hyperploid populations constituting 6% and 2% of the cells. The most striking difference between the DNA analyses and chromosome number distributions was that 13% of all metaphases were hyperploid with chromosome numbers outside the perimodal range but, except in one adenoma, without indication in the DNA histogram of corresponding hyperploid cell populations. We propose that these aberrant metaphases indicate an early acquired genetic instability of the neoplastic epithelium, which may be instrumental in generation of hyperploid, invasive clones, which constitute most colorectal carcinomas.