[Genesis, progression and prevention of human cancers]

Long-term studies of in vivo kinetics of growth and proliferation of human cancers in vivo have revealed that carcinomas become manifest in patients some 25 years after carcinogenetic process has begun (Fujita '78). During this long period of cancer growth, do cancer cells remain unchanged, in morphology and function? So far, few pathologists have attempted to answer the question. At late stages of cancer growth, human carcinoma cells show high degree of atypism so that correct diagnoses can always be established by microscopic examination of the atypism. By DNA quantification or karyotype analyses of individual cancer cells, however, we found that incipient cancers show much less DNA abnormalities than the advanced ones. It is now clear, from molecular studies (Fialkow '76) that, in principle, a human cancer starts from one mutated host cell. Histochemical studies revealed that the newborn cancer cell and their direct progeny, at least during the earliest stage of carcinogenesis, are diploid in DNA content and seem to show very little abnormalities. Obviously during the progression of cancer growth from the single cell to the final stage, gross changes are accumulated in the cancer cell genome so that highly atypical cells are constant final outcome of the human cancer growth in vivo. We analyzed abnormalities of chromosomal morphology together with DNA contents in advanced human cancer cells and found that, commonly, 10-20 chromosomal changes accumulate in individual cancer cells, thereby marked atypisms are produced in morphology and DNA contents in the cancer cells.(ABSTRACT TRUNCATED AT 250 WORDS)