DNA stemline heterogeneity in colorectal cancer

The current study was carried out on 88 colorectal carcinomas to assess the degree of intratumor heterogeneity as reflected by multiple aneuploid DNA stemlines and their relation to tumor stage and morphologic differentiation. Each tumor was segregated into an average of nine specimens (3-15), which were analyzed separately. DNA aneuploidies were identified in 72 cases (82%), 29 revealing multiple aneuploid DNA stemlines with up to four aneuploid subpopulations. In 10 of the 29 carcinomas with DNA stemline heterogeneity, a ratio of 2:1 was calculated from the different DNA indices, possibly indicating that the additional DNA stemline emerged from the first one by doubling its DNA content. No correlation was found between the overall frequency of DNA aneuploidies or heterogeneous DNA stemlines and the tumor stage according to Dukes' staging. Well-differentiated carcinomas tended to express aneuploid DNA stemlines more frequently than moderately or poorly differentiated tumors, although the morphologic intratumor heterogeneity did not correspond to the appearance of multiple aneuploid DNA stemlines. These data indicate a high degree of intraneoplastic diversity in colorectal cancer and emphasize the usefulness of DNA analyses for the quantitative assessment of tumor heterogeneity.