DNA mapping of colorectal neoplasms: a flow cytometric study of DNA abnormalities and proliferation.

BACKGROUND

There is some evidence that neoplastic development and progression evolve through a multistep process associated with hyperproliferation and genetic alterations. Therefore, changes of proliferation and of cellular DNA content within the adenoma-carcinoma sequence were studied.

METHODS

Using a "mapping" procedure, 12 adenomas and 18 carcinomas were analyzed flow cytometrically and histologically. In addition, normal mucosa adjacent to and distant from the tumors was assessed in the same way.

RESULTS

Of 59 adenomatous fractions, 35.6% (n = 21) were aneuploid, whereas the incidence of aneuploidy was 63.5% (54/85) in the carcinomatous sites. Additional tetraploidies were identified in 5 (8.5%) and 13 (15.3%) adenomatous and carcinomatous samples, respectively. Cell proliferation, as determined by the percentage of S-phase cells, was significantly (P < 0.001) higher in the carcinomatous specimens (14.8% +/- 0.8%; mean +/- SEM) than in the adenomatous ones (8.1% +/- 0.7%). It decreased to normal mucosa adjacent to (5.1% +/- 0.5%) and distant (5.3% +/- 0.6%) from the neoplasms. DNA mapping of the tumors revealed both distinct regions and extended areas of aneuploidy and tetraploidy. There is evidence from the mapping data that aneuploid populations arise at a single focus of the adenoma and expand over large areas before a subpopulation of cells acquires the capacity of invasion.

CONCLUSIONS

These data showing consecutive DNA content abnormalities within the colorectal adenoma-carcinoma sequence provide support for genomic instability and clonal evolution as important events of tumorigenesis and progression.