Prognostic value of S-phase fraction in lymph-node-negative breast cancer by image and flow cytometric analysis.
ABSTRACT Cellular DNA content and proliferation rates have been suggested as prognostic factors in breast carcinomas. A series of 271 lymph-node negative breast carcinoma patients without adjuvant therapy was reviewed (mean follow-up, 108 mo). Tumor cells from the same paraffin-embedded block tissue (Hedley's method) were analyzed by image analysis (IA) in Feulgen-stained smears and by flow cytometric analysis (FC). Clinicopathologic features, ploidy, S-phase fraction, and percentage of tumor cells with more than 5n DNA content (in diploid tumors, by IA) were related to outcome. The results of IA and FC were compared in 115 cases. Tumor size, histologic grade, desmoplasia and S-phase fraction were significant predictors of survival in multivariate analysis (Cox proportionate regression) (P < or = 0.03). Ploidy by the two methods showed agreement in 100 carcinomas (87%). Of the 15 discordant cases, FC detected 6 multiploid and 4 aneuploid-peridiploid. In contrast, IA detected more tetraploid carcinomas. Tumor size, histologic grade, desmoplasia, and S-phase fraction were independent predictors of long-term prognosis in our patients. Ploidy and percentage of tumor cells with more than 5n DNA content were not prognostic indicators. FC detected aneuploidy more frequently than did IA.
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ABSTRACT: SUMMARY In order to establish the relationship between ploidy, S-Phase fraction and morphological features in breast carcinoma, 402 frozen specimens were studied. No rela- tionship could be found when ploidy and S-phase fraction were correlated with lymph node status and patient's age. Aneuploid lesions were larger than diploid tumors and usually did not express hormone receptors. Infiltrat- ing duct carcinoma (322/402) showed a higher rate of aneuploidy and S-phase fraction related to the increase of the histological grade, scores of tubule formation, nuclear pleomorphism and mitotic rate. In a multivariate regression analysis the nuclear pleomorphism and tu- moral size were the only independent variables and most powerful predictive for aneuploidy in infiltrating duct carcinomas. DNA pattern and S-phase fraction are variables that correlate with morphological features, providing more objective and reproducible information.
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ABSTRACT: During the past decade, more than 300 articles, abstracts, and book chapters have been published about S-phase fraction (SPF) determined by DNA flow cytometry and its clinical utility for patients with breast cancer. However, the use of SPF for making treatment decisions for breast cancer patients remains controversial. After reviewing 273 published articles, we conclude: 1) Despite different techniques and cutpoints, correlations between SPF and other prognostic markers are relatively consistent across studies; higher SPF is generally associated with worse tumor grade, absence of steroid receptors, larger tumors, and positive axillary lymph nodes. 2) Higher SPF is generally associated with worse disease-free and overall survival in both univariate and multivariate analyses; SPF values from laboratories that have conducted validation studies can be used, in combination with other factors, to estimate the prognosis of patients with primary breast cancer. 3) There is considerable variability among laboratories regarding assay methodology, cell-cycle analysis techniques, and cutpoints for classifying and interpreting SPF; use of SPF values from different laboratories is problematic, and there remains a need for standardization of these processes and well-designed confirmation studies. We conclude that measurement of SPF does have clinical utility for patients with breast cancer, but standardization and quality control must be improved before it can be routinely used in community settings.Breast Cancer Research and Treatment 02/1998; 51(3):255-65. DOI:10.1023/A:1006188512927 · 4.20 Impact Factor
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ABSTRACT: To determine the importance of tumour DNA ploidy and cell proliferation, as measured by the S phase fraction (SPF), in relation to other established clinicopathological indicators of prognosis in breast cancer. A prospective study of 308 patients. Tumours were staged following the TNM system criteria and were classified according to the histological type and grade. DNA flow cytometry was performed on fresh/frozen samples stained with propidium iodide. Hormone receptors were analyzed by immunocytochemistry. A Cox proportional hazards regression model was used for statistical evaluation of the prognostic factors. Median follow up time was 39.6 months (range 3 to 84). A DNA diploid pattern was found in 134 tumours (43.5%) and aneuploid in 174 (56.5%). Median SPF value was 6.1% (range 1% to 27.8%). DNA ploidy and SPF were strongly correlated (p < 0.001), and both were related to histological type (p < 0.001), grade of differentiation (p < 0.001), tumour size (p = 0.006 and p = 0.002), and hormone receptor activity (p < 0.001). DNA ploidy was also related to node status (p = 0.022), but SPF was not. In univariate analysis, there were significant correlations between disease-free survival and age, histological grade, tumour size, node status, DNA ploidy, SPF, and hormone receptor activity; age, tumour size, node status, DNA ploidy, and hormone receptors were predictors of overall survival. In multivariate analysis, only node status (p = 0.001) and DNA ploidy (p = 0.006) retained independent prognostic significance in relation with overall survival, while node status (p < 0.001) and SPF (p < 0.001) were predictors of disease-free survival. DNA ploidy and SPF continued to predict disease-free and overall survival in lymph node positive (pN1) patients but not in the lymph node negative (pN0) group. DNA ploidy and SPF are strongly intercorrelated and have independent prognostic value for predicting the short term clinical outcome of breast carcinoma patients.Journal of Clinical Pathology 09/1999; 52(8):604-11. DOI:10.1136/jcp.52.8.604 · 2.55 Impact Factor