Evidence for the existence of the stages of initiation and promotion in the human have come largely from clinicopathological and epidemiological studies. That initiation occurs in the hu- man is evidenced by the spontaneous incidence of cancer in the human population, implying initiation as an essential component for the development of such neoplasms. Evidence for the existence of the stage of promotion in human neoplasia is not so definitive as that seen in the animal, but since the pathogenesis of cancer development in the human may be recapitulated in the animal, one may use such model systems to potentially identify the stage of promotion in the development of human neoplasia.
Morphological evidence for the clonal expansion of initiated cells during tumor promotion is based on the description of preneoplastic lesions and attempts to relate such lesions to the development of specific malignancies (cf. Henson and Albores-Saavedra, 1986; Dunham, 1972). Table 7.11 lists some preneoplastic lesions of the human and their related or analogous lesions in the rodent. The preneoplastic nature of the human lesions has been inferred from both histo- pathological and epidemiological studies. The similarity of putative human preneoplastic lesions to comparable lesions known to be preneoplastic that develop in experimental animal models further supports the preneoplastic nature of the human alterations. For example, nodular hyper- plasia of the adrenal cortex is quite commonly seen in the rodent, and the preneoplastic potential of the lesions has been implied for many years in the animal (Dunn, 1970). The lesions observed in mammary carcinogenesis are also quite analogous in animals and humans (van Bogaert,1984). In addition, the lesions observed in the liver and colon of animals are strikingly similar to their human counterparts. Although examples exist where the congruence of the preneoplastic counterpart in the human is not distinct during pathogenesis of the developing neoplasm in ani- mals (e.g., the dysplastic nevus to malignant melanoma), in general the similarities of preneo- plastic lesions in the human and experimental animal strongly argue that the stages of the carcinogenic process in mammals are very similar across species.