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

“…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.…”

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confidence: 99%

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

Fernö¹,

Baldetorp²,

Ewers³

et al. 1992

Cytometry

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Flow cytometric assessments of DNA ploidy status and the S-phase fraction (SPF) have been shown to yield prognostic information in breast cancer. The aim of the present investigation was to elucidate the reproducibility of results with regard to tumor DNA heterogeneity, and to ascertain whether the prognostic value of DNA measurements might be enhanced by analyzing two pieces of a tumor instead of one.Agreement with regard to ploidy status (diploid versus non-diploid) was obtained in 90% of cases (71/79) when two adjacent sections of the tumor were investigated, and in 77% of cases (10/13) when four biopsies from different quadrants of the tumor specimen were investigated. The corresponding figures for agreement in SPF (divided into three categories, < 7.0%, 7.0-11.9%, and > 12%) were 75% 69/79; 2-sample series) and 55% (7/13; 4-biopsy series).The main reason for variance in ploidy results was the difficulties in distinguishing near diploid cell populations. Discrepancies in SPF categories could be explained by minor fluctuations in SPF values near the cut-off levels, or by variance in ploidy status, the fraction of nondiploid nuclei, and background noise due to cell debris.There was a stepwise increase in recurrence rate (RR) among patients with increasing SPF category (RR: 20%, 41%, and 53%). Patients whose SPF categories varied, from low or intermediate in one part of the tumor to high in another, seemed to have a poor prognosis (RR = 57%).We conclude that the variation in ploidy status and SPF between different parts of the same tumor specimen is largely to be explained by uncertainty in the interpretation of the DNA histograms and by difficulties inherent in the estimation of SPF, rather than by the existence of DNA tumor heterogeneity. Evaluation of a different part of the same tumor specimen may be of value, especially in the case of SPF, as this may yield additional prognostic information. These findings also emphasize the need for good quality control of FCM DNA analysis.

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“…It was impossible to extend the comparison to the whole series because of either insufficient material or technical problems but, in view of our results on the 64 cases and the association between SPF and histological grade already established for our samples (O'Reilly et al, 1990), we considered that the number of cases with results by both methods was sufficient to confirm MIB 1 immunohistochemistry as a good marker of proliferative activity. Others have confirmed this finding and also shown that MIBI is strongly associated with other recognized markers of proliferation, including mitotic count and Ki-67 expression (Lipponen et al, 1992;McCormick et al, 1993;Ellis et al, 1996).…”

Section: Resultsmentioning

confidence: 91%

Cell proliferation measured by MIB1 and timing of surgery for breast cancer

Cooper

Gillett²,

Smith³

et al. 1998

Br J Cancer

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Summary We have investigated the use of the antibody MIBl as a proliferative and prognostic marker in breast cancer and whether changes in proliferative activity could account for differences in prognosis of premenopausal women operated on during different phases of the menstrual cycle. MIBl expression was strongly correlated with S-phase fraction and histological grade. There was no difference in MIBl scores between different phases of the menstrual cycle. Both MIBl score and timing of surgery correlated significantly with duration of survival, while the two together were even stronger predictors of overall survival. Women with slowly proliferating tumours surgically removed in the luteal phase had a very good prognosis, whereas women with rapidly proliferating tumours excised at other times of the cycle had a worse prognosis.

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

Abstract: Summary DNA index and S-phase fraction (SPF) were Multivariate analysis using the Cox model suggested that, while SPF gave prognostic information independent of tumour size or nodal status, this independent significance was lost when histological grade was included in the analysis.

Cited by 105 publications

References 16 publications

Predicting outcome for patients with node negative breast cancer: a comparative study of the value of flow cytometry and cell image analysis for determination of DNA ploidy

Predicting outcome for patients with node negative breast cancer: a comparative study of the value of flow cytometry and cell image analysis for determination of DNA ploidy

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

Cell proliferation measured by MIB1 and timing of surgery for breast cancer

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