Independent prognostic value of ploidy in colorectal cancer: a prospective study using image cytometry

Ploidy is the state of a cell's chromosome complement. Normal human cells, in which the chromosomes are organized as 23 pairs, are diploid, while germ cells with 23 single, unpaired chromosomes are haploid. Pathological aneuploid states may be observed in some cancer cells, and much research effort is being expended on the relation of the ploidy observed in cancer patients' cells and the outcome of disease. In many, though by no means all, cases, aneuploidy correlates with a poorer prognosis. The chromosome complement of a cell is determined directly by karyotyping, which requires living cells and is generally done with fresh white blood cells. In other tissues, the ploidy is estimated my measuring the DNA content. Since many medical laboratories possess flow cytometric equipment, flow cytometry is the most popular method for measuring DNA content. However, microscopic image analysis may be used as well. Researchers have used image analysis to measure the DNA content of cells scraped from fresh surgical specimens of colorectal cancers. DNA was measured photometrically by measuring the optical density of the cell nucleus after staining with the classic Feulgen reaction. The histogram of DNA measurements of individuals cells for each cancer was evaluated to estimate the ploidy of the cancer. The ploidy measurement was found not to relate to age, histologic grade, Dukes' stage, or serum levels of carcinoembryonic antigen. When cancer ploidy was evaluated in 211 cases, it was found to be an independent predictor of prognosis, with aneuploid cancers carrying a worse prognosis. In keeping with previous studies that utilized flow cytometry, aneuploidy was observed more frequently in distal colorectal cancer than in proximal cancer. However, in a multivariate analysis of prognosis, ploidy did not significantly add to the predictive ability of other features when the Dukes' stages were included in the analysis. (Consumer Summary produced by Reliance Medical Information, Inc.)