The prognostic significance of nuclear DNA content in invasive breast cancer – a study with long-term follow-up

Abstract

Summary The nuclear DNA content of 351 breast carcinomas was determined by flow cytometry from paraffin-embedded tissue to assess the prognostic significance of DNA ploidy, the DNA index (DI) and the S-phase fraction (SPF). The minimum follow-up of the patients was 22 years, and they were all from a defined urban population. DNA ploidy correlated with histological type and grade, mitotic count and nuclear pleomorphism (P<0.0001), and also with axillary nodal status (P=0.0005), tumour necrosis (P=0.001), primary tumour size (P = 0.03), menopausal status (P = 0.004) and the presence of distant metastases at the time of the diagnosis (P = 0.04). Survival corrected for intercurrent deaths of the patients with a diploid tumour was better than that of the patients with a non-diploid tumour (P = 0.0001, 48% vs 28% at 25 years). SPF Leatham & Brooks, 1987; Slamon et al., 1987).The nuclear DNA content determined by flow cytometry has recently emerged as a new prognostic factor in breast cancer. The technique has gained some popularity, since flow cytometric histograms are rapid to produce and often easy to interpret. It has been suggested that breast carcinomas with an abnormal (non-diploid or aneuploid) nuclear DNA content are associated with less favourable prognosis than carcinomas with a normal (diploid) DNA content (Hedley et al., 1984(Hedley et al., , 1987Coulson et al., 1984;Ewers et al., 1984;Thorud et al., 1986;Baildam et al., 1987;Cornelisse et al., 1987;Kallioniemi et al., 1987;Stal et al., 1989). Similarly, the DNA index (DI, the relative DNA content of an aneuploid stemline of cells as compared with diploid cells) and the percentage of S-phase cells in the DNA histogram (S-phase fraction, SPF) have been found by some to be of prognostic significance (Dowle et al., 1987;Hedley et al., 1987;Kallioniemi et al., 1988;Stal et al., 1989;McDivitt et al., 1986;Klintenberg et al., 1986). However, the prognostic value of nuclear DNA content analysis is still unsettled. Some authors report DNA content to be the most important prognostic variable in breast cancer, and to have independent prognostic value in a multivariate analysis , whereas others find it to have prognostic value only in a univariate analysis (Stal et al., 1989;Hedley et al., 1984), and yet a few fail to find any prognostic significance at all when overall survival is concerned (van der Linden et al., 1989;Uyterlinde et al., 1988;Owainati et al., 1987

Optimizing flow cytometric DNA ploidy and S‐phase fraction as independent prognostic markers for node‐negative breast cancer specimens

“…The near-hyperdiploid DI threshold of 1.13 (PA2) is not a new observation and similar thresholds have been reported elsewhere (25,48). This relatively high DI threshold perhaps explains the relative success of low-resolution technologies in showing DNA ploidy as a strong prognostic variable (49,50).…”

“…In the 1980s, hundreds of flow cytometry papers demonstrated prognostic significance of DNA ploidy and/or S-phase for many types of solid tumors (16 -22). In particular, many studies showed that S-phase and, in some cases, DNA ploidy could stratify node-negative breast cancer patients into low-and high-risk groups for relapse and death (23)(24)(25), potentially giving oncologists more options in treating this prevalent and deadly disease. Unfortunately, many studies found that S-phase and DNA ploidy were highly correlated.…”

Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma

“…All hospitals, practising physicians and pathological laboratories are requested to report to (WHO, 1981). ILCs were categorized as either 'classical' (n = 157) or 'variant' forms (n = 60) using the criteria published previously (Fechner, 1975;Fisher et al, 1977;Martinez and Azzopardi, 1979 DNA flow cytometry DNA ploidy of 637 carcinomas had been determined by flow cytometry as described previously in conjunction with another study of paraffin-embedded tissue (Toikkanen et al, 1989). The Table 2.…”

Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients

“…This is especially relevant amongst node-negative patients showing a 5-year breast cancer survival rate of 90% (Carter et al, 1989). A growing number of reports indicate that hormone receptor status and proliferative indices could be used to predict the rate of recurrence and survival (Clark et al, 1989;Crowe et al, 1982;Godolphin et al, 1981;Hatschek et al, 1989;Sigurdsson et al, 1990;Skoog et al, 1987;Spyratos et al, 1989;Stal et al, 1989;Thorpe et al, 1987;Toikkanen et al, 1989). While S-phase fraction has been related to the recurrence-free survival of systemically untreated patients with breast cancer (Hery et al, 1987;Silvestrini et al, 1989), conflicting results have been presented on the prognostic value of hormone receptors in the same group of patients.…”

“…A suspension of isolated nuclei was prepared without washing steps as described by Vindelov et al (1983). The procedure included treatment with a detergent (0.1% NP40), trypsin and RNAse followed by filtering through a 41 ytm nylon mesh.…”