A new hypothesis on the natural history of bladder cancer based on the study of tumor DNA levels by flow cytometry

72 bladder tumors were studied for nuclear DNA content with flow cytometry. A bimodal DNA profile was present in 33 of them (45%). The following findings concerning the aneuploid second peak of these 33 tumors are remarkable. Aneuploid peak DNA index distribution is discontinuous: there is no peak below 1.5 nor between 2.3 and 2.7. Aneuploid peak importance (second peak cell percentage versus all tumor cells in the same sample) increases when its DNA index decreases from 2.0 to 1.5 = this percentage is on average 45% for a DNA index of 2.0 and increases to 75% when DNA index decreases to 1.5. Aneuploid peak mitotic activity increases when DNA index decreases from 2.0 to 1.5 = the percentage of S G2 M cells of the aneuploid peak is in the range of 15% for a DNA index of 2.0 and in the range of 22% for a DNA index of 1.5. These findings are in favor of a dynamics in bladder cancer natural history. Tumors are supposed to share the same clonal evolution, in 3 stages. First stage: transformed tumor cell DNA profile is unimodal with a DNA index in the region of 1; second stage: due to chromosomic non-dysjunction during mitosis, a second peak appears with a DNA index of 2. Third stage: DNA index of this aneuploid second peak progressively decreases from 2 to 1.5 as a consequence of non vital chromosomes loss by tumor cells. It is suggested that DNA index as defined by flow cytometry does not have an absolute prognostic value per se, but in combination with tumors mitotic activity.(ABSTRACT TRUNCATED AT 250 WORDS)