Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer

Abstract

SummaryDNA Ploidy and S phase fraction (SPF) were measured in Stage I and II breast cancers from patients with at least 8 years of follow-up, to assess the prognostic significance of these data. Disaggregated sections of formalin-fixed, paraffin-embedded tumour were analysed by flow cytometry. SPF was calculated using a rectangular model of S phase, after subtraction of background debris using an exponential model. 64% of tumours were DNA aneuploid. The median SPF was 4.5% for DNA diploid, and 10.9% for DNA aneuploid tumours. There were small reductions in survival at 10 years for DNA aneuploid tumours, and for tumours with above median SPF, but these were not statistically significant. The relative hazard for DNA aneuploid tumours was 1.20 (95% CI 0.81-1.76), and for high SPF was 1.31 (95% CI 0.87-1.98). Neither factor was statistically correlated with survival in multivariate analysis. Technical and theoretical factors limit the accuracy and reproducibility of flow cytometric data, and may explain the lack of prognostic information given.Since the publication of a technique for using paraffin embedded tissue for flow cytometry (Hedley et al., 1983) (Hedley et al., 1985). All presumptively DNA aneuploid histograms showed a substantial population of DNA diploid cells, which acts as an internal standard. Histograms were classified as DNA aneuploid if more than one discrete population was identified. The DNA index was then assigned as the ratio between the mean channel number for the aneuploid GO/GI peak, and the mean channel for the GO/GI peak of the normal cell population within the histogCorrespondence:

The prognostic significance of DNA flow cytometry in breast cancer: results from 881 patients treated in a single centre

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S_q In this single-centre study of 881 patients, S-phase fraction (SPF) was shown to be a sgnifiant prognostic marker in terms of ovrll suvival (OS), rdapse-free survival (RFS) A further stimulus to publish our data came from two recent reports which failed to find a prognostic role for SPF in breast cancer (Stanton et al, 1992; Silvestini et al, 1993

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“…Further tumour samples were studied for comparison of flow cytometric parameters with other tumour characteristics such as histological grade (Masters et al, 1987) and c-erb-B-2 expression (Banes et al, 1992) or for analysis of the effects of different fixation methods on flow cytometric analyses (Gilkett et al, 1990). These A further stimulus to publish our data came from two recent reports which failed to find a prognostic role for SPF in breast cancer (Stanton et al, 1992;Silvestini et al, 1993 outcome. The mean age of the patients was 55.9 (range 21-94) years.…”

DNA Flow Cytometry but Not Telomerase Activity as Predictor of Disease-Free Survival in pT1–2/N0/G2 Breast Cancer

“…The finding corroborates our previous data on a large series of 308 unselected breast cancer patients [12] , in which DNA flow cytometry was found to be a predictive factor in the identification of low-and high-risk subgroups, allowing better stratification of individual patients for appropriate treatment. On the contrary, however, some previously published studies that investigated large series ( 1 300 patients) with long follow-up ( 1 5 years median) did not demonstrate the significant prognostic value of DNA flow cytometry in breast cancer [13][14][15] . Technical pitfalls relat- ed with lack of standardized procedures, different sampling sources, difficult interpretation of DNA histograms and DNA intratumoral heterogeneity limit the accuracy and reproducibility of flow cytometric data, and may explain the controversial results obtained.…”

Analysis of DNA and morphometry in breast carcinoma

“…However, the prognostic value of DNA parameters has been questioned (Utyerlinde et al 1989;Stanton et al 1992). A range of additional DNA histogram parameters has also been reported to yield prognostic information in breast cancer (Böcking et al 1984;Opfermann et al 1987;Stenkvist and Strande 1990).…”