Tumour DNA ploidy as an independent prognostic factor in breast cancer

Abstract

Summary We determined nuclear DNA content from 308 archival paraffin-embedded malignant breast tumours and evaluated the survival of the patients by univariate and multivariate statistical analyses. The overall 8-year survival rate of stage I-III breast cancer patients was 74.3% in DNA-diploid and 51.2% in DNA-aneuploid tumours (P<0.0001). DNA ploidy had prognostic significance in both node-negative and node-positive breast cancer Dowle et al., 1987;Kallioniemi et al., 1987a) and the content of oestrogen and progesterone receptors (Bichel et al., 1982;Moran et al., 1984;Coulson et al., 1984;Horsfall et al., 1986;Kallioniemi et al., 1987a). Whether DNA ploidy is an independent prognostic indicator or merely related to other prognostic factors is unclear (McGuire & Dressler, 1985;Cornelisse et al., 1987;Dowle et al., 1987).In the present study we evaluated the clinicopathological correlations and prognostic value of DNA DNA flow cytometry Paraffin-embedded tumours were processed for DNA flow cytometry by a previously described modification (Kallioniemi et al., 1987a) of the method of Hedley and coworkers . Briefly, 50 jgm sections from the paraffin-embedded tumours were dewaxed with xylene, rehydrated and digested overnight with trypsin. One to 6 sections from different parts of the primary tumour were processed for DNA flow cytometry. The nuclear suspension was stained with ethidium bromide, digested with RNAase and analysed with an EPICS C flow cytometer using 488 nm excitation. DNA index of aneuploid peaks and the coefficient of variation (CV) of all DNA peaks were Correspondence: O.-P. Kallioniemi.

DNA index, S-phase fraction, histological grade and prognosis in breast cancer

“…Patients whose tumours have a low proportion of cells in S phase do appear to have a better prognosis (Kallioniemi et al, 1986). Recent reports also show a relapse-free survival and survival advantage for patients with diploid tumours (Cornelisse et al, 1987;Hedley et al, 1987;Kallioniemi et al, 1987), although this finding is not universal (Klintenberg et al, 1986), and may be confined to sugroups defined by other prognostic factors (Cornelisse et al, 1987).…”

A prognostic score in histological node negative breast cancer

“…Such information cannot be obtained from univariate analyses. Few multifactorial studies on N -breast cancer have been published (Bauer et al, 1983;Clark & MacGuire, 1986;Dressler et al, 1987;Kallioniemi et al, 1987;Parl et al, 1984;Sears et al, Silvestrini et al, 1986;Thorpe et al, 1987;Trojani et al, 1987;Tubiana et al, 1984). High nuclear grading (Bauer et al, 1983), high histological grading (Sears et al, 1982;Stewart et al, 1983;Trojani et al, 1987;Tubiana et al, 1984), tumour size >5 cm (Clark & MacGuire, 1986;Kallioniemi et al, 1987;Mason et al, 1983;Tubiana et al, 1984), tumour necrosis (Bauer et al, 1983), macroscopic invasion of skin by the tumour (Sears et al, 1982), lymph node hyperplasia (Bauer et al, 1983), negative oestrogen receptors (Clark & MacGuire, 1986;Mason et al, 1983;Parl et al, 1984), negative progesterone receptors (Kallioniemi et al, 1987;Mason et al, 1983) are independent prognostic factors that may explain N-breast cancer recurrences reported in the literature.…”

One or multiple samplings for flow cytometric DNA analyses in breast cancer‐prognostic implications?

“…Flow cytometric measurement of DNA content per nucleus provides information both about DNA ploidy status and about proliferative activity as represented by the fraction of cells in the S-phase of the cell cycle, The prognostic value of DNA ploidy has been demonstrated in many studies (6,8,9,20,24,42), as has that of the S-phase fraction (SPF; 13,15,16,22,31,37), though others have failed to confirm the independent prognostic value of these variables (12,21,30). sults.…”