Abnormal DNA content as a biomarker of large bowel cancer risk and prognosis

Abstract

Aneuploid cell populations can be defined as those that contain an abnormal number of chromosomes or an abnormal amount of DNA. Aneuploidy can be reliably detected by flow cytometric analysis of DNA content. This technique not only identifies aneuploid cell populations but can also quantify the percent of cells in various phases of the cell cycle, thus giving an indication of the proliferative activity of a tissue. Aneuploidy occurs in approximately 60% of established colorectal cancers, and many studies have demonstrated that patients with aneuploid tumors have a poorer prognosis than patients with diploid colon cancers. Some studies have suggested that the proliferative rate of tumors, as assessed by the percent of cells in S phase, also has prognostic significance. Until recently, aneuploidy was thought to occur only in malignant tissues, but it has been clearly shown that aneuploid cell populations can be identified in benign adenomatous polyps as well as in non-neoplastic-appearing mucosa of patients with chronic ulcerative colitis and Barrett's esophagus. In chronic ulcerative colitis, aneuploidy occurs more frequently in patients with dysplasia or cancer than in those with no evidence of neoplasia. Similarly, dysplastic and malignant biopsies are more commonly aneuploid than non-neoplastic biopsies. Patients who have undergone colectomy for cancer or dysplasia in the setting of chronic ulcerative colitis frequently have multiple areas of aneuploidy throughout the remainder of their colon. Whether aneuploidy can be useful as a marker of cancer risk in patients with chronic ulcerative colitis deserves further investigation.