Nurten Gunduz

DNA flow cytometric analysis of primary operable breast cancer. Relation of ploidy and S-Phase fraction to outcome of patients in NSABP B-04

Between 1971 and 1974, 1665 women with primary operable breast cancer were randomized into a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial (B‐04) conducted to evaluate the effectiveness of several different regimens of surgical and radiation therapy. No systemic therapy was given. Cells from archival paraffin‐embedded tumor tissue taken from 398 patients were analyzed for ploidy and S‐phase fraction (SPF) using flow cytometry. Characteristics and outcome of patients with satisfactory DNA histograms were comparable to those from whom no satisfactory cytometric studies were available. In patients with diploid tumors (43%), the mean SPF was 3.4% ± 2.3%; in the aneuploid population (57%), the SPF was 7.9% ± 6.3%. Only 29.9% ± 17.3% of cells in aneuploid tumors were aneuploid. Diploid tumors were more likely than aneuploid tumors to be of good nuclear grade (P less than 0.001) and smaller size (P equals 0.03). More tumors with high SPF were of poor nuclear grade than were tumors with low SPF (P equals 0.002). No significant difference in 10‐year disease‐free survival (P equals 0.3) or survival (P equals 0.1) was found between women with diploid or aneuploid tumors. Patients with low SPF tumors had a 13% better disease‐free survival (P equals 0.006) than those with a high SPF and a 14% better survival (P equals 0.007) at 10 years than patients with high SPF tumors. After adjustment for clinical tumor size, the difference in both disease‐free survival and survival between patients with high and low SPF tumors was only 10% (P equals 0.04 and 0.08, respectively). Although SPF was found to be of independent prognostic significance for disease‐free survival and marginal significance for survival, it did not detect patients with such a good prognosis as to preclude their receiving chemotherapy. The overall survival of patients with low SPF was only 53% at 10 years. These findings and those of others indicate that additional studies are necessary before tumor ploidy and SPF can be used to select patients who should or should not receive systemic therapy.

CYTOKINETICS OF TUMOUR AND ENDOTHELIAL CELLS AND VASCULARIZATION OF LUNG METASTASES IN C3H/HE MICE

A model of lung metastases was developed using intravenous injection of tumour cell aggregates of spontaneous C3H/He mammary tumours in syngeneic mice. the growth rate of lung tumours decreased with increasing tumour volume, with mean host survival of 46 days. the cytokinetics of individual tumours ranging between 0.004 and 4.2 mm3 in volume were studied. the labelling index (LI) ranged between 12 and 17%, the DNA synthesis time (Ts) being 9–10 hr. the growth fraction (GF) ranged between 26 and 38%. the cell cycle time (Tc) was found to be 18–19 hr. the LI and the GF decreased with increasing tumour volume doubling time (Td). No correlation was found between the tumour volume and Tc. the LI of endothelial cells within these tumours, ranging between 0.004 and 4.2 mm3 in volume was 14–15% and endothelial cell proliferation was not affected by tumour growth.