Flow cytometric DNA hypertetraploidy is associated with unfavourable prognostic features in breast cancer.

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Abstract
Breast tumours with a DNA content higher than 4N (hypertetraploidy) are not well characterised. The aim of this study was to evaluate the clinical and biological characteristics of 51 hypertetraploid breast carcinomas selected from a series of 860 consecutive cases analysed by flow cytometry. The clinicopathological characteristics of the hypertetraploid group were compared with those of a control group of 138 non-hypertetraploid breast carcinomas. Breast tumours from patients submitted to surgery as primary therapeutic approach (15 hypertetraploid and the 138 non-hypertetraploid) were TNM staged and classified according to the histological type and grade. The remaining 36 patients had advanced neoplastic disease at presentation and were classified by cytological criteria only. DNA flow cytometric analysis was performed on fresh-frozen samples stained with propidium iodide. Hormone receptors were analysed by immunocytochemistry. The incidence of hypertetraploid breast tumours was 5.9% (51 of 860). All the patients were women and the mean age at diagnosis was 65 years. There was a family history of breast cancer in 21.6% of cases. In the group of operated patients, 33.3% had pT3 tumours and 53.3% had axillary lymph node metastases. All but one tumour were invasive ductal carcinomas; the remaining was an invasive papillary carcinoma. Ten (66.7%) tumours were classified as poorly differentiated carcinomas. Oestrogen and progesterone receptors were negative in 33 (64.7%) and 38 (74.5%) tumours, respectively. At last follow up, 35 (72.9%) patients were alive, while 13 (27.1%) died of disease within three years of diagnosis. Statistical comparison of the clinicopathological features of hypertetraploid v non-hypertetraploid breast carcinomas yielded a significant difference in tumour size (p < 0.001), histological grade (p < 0.001), hormone receptor status (p < 0.001), and overall survival (p < 0.001) between the two groups. Flow cytometric DNA hypertetraploidy is related to clinicopathological features of breast cancer usually associated with unfavourable prognosis.