Evolution of DNA ploidy state and DNA index in colorectal adenomas and carcinomas using the crypt isolation technique: New hypothesis in colorectal tumorigenesis

The evolution of DNA diploid, aneuploid and multiploid (diploid and aneuploid) states that represent DNA types that are independent of genetic alterations in colorectal tumors were examined. Changes in the DNA index (DI) accompanying tumor development from adenoma to carcinoma were assessed. In colorectal adenomas and early cancers, the DNA was diploid or multiploid. A pure aneuploid state was observed in advanced carcinomas only, whereas the aneuploid DI values of adenomas were characterized by two distinct peaks. The DI values for the carcinomas were randomly distributed. However, in advanced carcinomas, aneuploid carcinomas tended to have lower DI whereas aneuploid populations within multiploid carcinomas tended to have higher DI. Early cancers were subdivided into two groups: a cancer region associated with an adenomatous region (group A tumors) and a cancer region that exhibited an absence of or a very limited adenomatous region (group B tumors). Group A tumor DI were lower than group B. It is suggested that low DI adenomas might transform into group A tumors, which consequently progress to advanced aneuploid carcinomas. In addition, group B tumors might derive predominantly from high DI adenomas or from group A tumors by high DI evolution, and might progress into advanced multiploid carcinomas. Therefore, the evolution of the DNA index might play an important role in the development of colorectal tumors.