DNA ploidy status and prognosis in colorectal cancer: A meta-analysis of published data

Purpose: In colorectal cancer, the negative effect of aneuploidy has been a controversy for more than 20 years. Studies to determine a survival-deoxyribonucleic acid content relationship have conflicting results. A systematic literature search followed by a meta-analysis of published studies addressing prognostic effect of aneuploidy for patients who underwent surgical treatment of colon and rectal cancer was conducted. Methods: The main outcome measure was the five-year overall mortality rate after surgical resection. For the selected studies, we estimated this outcome for three subsets of patients through separate meta-analyses: 1) for all patients with colorectal cancer; 2) only between patients with Stage II colon cancer; and 3) only for studies in which follow-up losses were declared. The presence of publication bias was assessed with a funnel plot for asymmetry. Results: A total of 5,478 patients with colorectal cancer were represented in 32 studies (Group 1), we estimated a reduction in the five-year overall mortality from 43.2 percent for aneuploid tumors to 29.2 percent for diploid tumors (combined relative risk=1.44; 95 percent confidence interval=1.34-1.55; P < 0.001). In addition, 357 patients with Stage II colon cancer (Group 2) extracted from three studies had an absolute reduction of 14.3 percent in five-year overall mortality favoring diploid tumors (combined relative risk=1.93; 95 percent confidence interval=1.29-2.89; P=0.001). Lastly, of 14 studies in which follow-up losses were declared (Group 3), 2,221 patients were represented and a 15.7 percent mortality reduction was measured favoring patients with diploid tumors (combined relative risk=1.44; 95 percent confidence interval=1.3-1.61; P < 0.001). Conclusions: Patients who undergo an aneuploid colorectal cancer surgical resection have a higher risk of death after five years. This finding may ultimately impact survival of patients with node-negative colon cancer through adjuvant therapy.