Ian W. Taylor

Tamoxifen induces accumulation of MCF 7 human mammary carcinoma cells in the G0/G1 phase of the cell cycle.

When MCF 7 human mammary carcinoma cells in exponential growth phase were treated with tamoxifen a dose-dependent inhibition of cell growth was observed. This inhibition was accompanied by a dose-dependent decrease in the percentage of S phase cells and a concomitant increase in the percentage of cells in the G0/G1 phase of the cell cycle. Simultaneous treatment of cultures with a 10-fold lower concentration of oestradiol completely reversed the growth inhibitory and cell cycle effects of tamoxifen at doses below 5 microM but only partially reversed the effects of higher doses of this drug. It is concluded: (1) that tamoxifen-induced growth inhibition is associated with major changes in the cell cycle kinetic parameters of MCF 7 cells, indicating that this drug is a cell cycle phase-specific growth inhibitory agent and (2) that not all the anti-proliferative and cell cycle effects of tamoxifen in vitro are reversed by simultaneous treatment with oestradiol. This suggests that tamoxifen, in addition to having effects on cell proliferation that are reversed by oestrogens and are likely to be oestrogen receptor-mediated, has antitumor activity in vitro that involves biochemical mechanisms independent of the oestrogen receptor system.

Flow cytometric analysis of cellular DNA content as an adjunct to the diagnosis of ovarian tumours of borderline malignancy

Summary Flow cytometric analysis of cellular DNA content was performed on tissue from 44 borderline ovarian tumours (tumours of low malignant potential). Forty‐two tumours (95%) were diploid and associated with both an indolent biological behaviour and good prognosis. Aneuploidy was identified in only 2 tumours (5%), and one of the associated patients died of progressive disease within months of the initial diagnosis. Careful review of the histopathology of these 2 aneuploid tumours revealed areas of invasion in the omental and peritoneal “implants” of each. This study has reinforced the currently advocated separation of so‐called borderline tumours from invasive ovarian carcinomas and the interpretation of the pathological criteria used to categorize such neoplasms. Our results indicate that flow cytometric analysis of cellular DNA content may complement conventional histopathological diagnosis by providing an objective parameter which correlates with biological behaviour and may identify the few genuine borderline ovarian epithelial neoplasms which show clinical progression.

The influence of age on the DNA ploidy levels of breast tumours

Primary tumour DNA content and estimates of cell cycle kinetic parameters were analysed by flow cytometry in 114 cases of breast cancer. Tumours were classified as: near-diploid, single aneuploid, tetraploid and greater, and multiploid (defined as having more than one aneuploid tumour cell population). No significant correlations were found between ploidy and histologic type, tumour size, lymph node involvement or receptor (oestrogen and progesterone) status. a highly significant correlation between ploidy and proliferative activity (as assessed by the percentage of cells in S phase) was observed, with near-diploid and diploid tumours being associated with a low (less than or equal to 10%) S phase fraction (P = 0.0001). A marked relationship between ploidy and patient age was also seen, with increased DNA content being associated with older patients (P = 0.025). In contrast, no patients with multiploid tumours were over 60 yr, and their age distribution was significantly different from the population as a whole (P less than 0.05), suggesting that multiploidy might be a phenomenon associated with the menopause.

Measurement of cellular DNA content as an adjunct to diagnostic cytology in malignant effusions

We reviewed the final diagnosis and outcome of 119 patients who developed serous effusions. In addition to routine cytological examination, the cellular DNA content of fluid samples aspirated from the effusions was measured using flow cytometry in order to determine whether the detection of aneuploid cells could aid in diagnosis or serve as a guide to prognosis. The final diagnosis of 35 patients was non-malignant and a further 40 patients with biopsy-proven cancer had cytologically negative effusions. In all of these cases flow cytometry revealed the presence of diploid cells only. The effusions from 36 cancer patients were reported by cytology to contain a variable proportion of malignant cells, and aneuploid cells were detected in 23 of these samples, the remainder containing only diploid cells. Of 8 effusions where cytology was equivocal, one contained aneuploid cells and clinical outcome subsequently showed that all 8 were malignant. Median survival of patients with cancer was 3 months, and a positive cytology had no influence on survival. However, of the patients with positive cytology, those whose effusions contained aneuploid cells had a poorer short-term prognosis than those cases where only diploid cells could be detected (median survival 1.5 vs 4 months). Measurement of cellular DNA content using flow cytometry can occasionally confirm cancer in a cytologically equivocal effusion, but the negative results in 13 out of 36 (36.1%) effusions where cytology was reported as positive suggests that it has only a limited role in this clinical setting, using currently available techniques.