Tumor Progression Studied by Analysis of Cellular Features of Serial Ascitic Ovarian Carcinoma Tumors

Seven consecutive ascitic tumors were obtained over a 9-month period from a patient with serous adenocarcinoma of the ovary. The tumor cell populations were analyzed for cellular proliferation (labeling index, agar clonogenicity, and self-renewal capacity), for cell differentiation (cell surface expression of carcinoembryonic antigen and histochemical stain for fat accumulation), and for karyotypic changes. Evidence is presented of increased aggressiveness of proliferative features together with a decreasing proportion of cells with differentiated features. Parallel temporal changes were documented in density-volume characteristics of the tumor cell population, from small, high-density to large, low-density cells. The only karyotypic change identified over this period was the loss of one X-chromosome and the increased frequency of cells containing double minute bodies. The progressive characteristics described in this human tumor are not, therefore, associated with gross chromosomal changes. The accumulation of double minute chromosome bodies may be associated with a low-dose methotrexate exposure or with the tumor progression.