DNA Ploidy is an Independent Prognostic Biomarker in Breast Invasive Ductal Carcinoma

António E Pinto, Teresa Pereira, Giovani L Silva, Mónica C Ferreira, Saudade André

Abstract


Objective: To evaluate ‘classic’ prognostic parameters, as well as DNA ploidy and S-phase fraction, in relation to disease-free andoverall survival in breast invasive ductal carcinoma with long-term follow-up.Material and Methods: The study involved 400 patients with breast invasive ductal carcinoma and median follow-up of 134 months(50-240). Histological grading, tumour size, axillary nodal involvement, pathological staging and hormone-receptor status were assessedas established prognostic markers. Ploidy and S-phase fraction were determined prospectively by DNA flow cytometry usingfresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables.Results: There were 106 deaths (26.5%) and 141 disease recurrences (35.2%) during follow-up. Two hundred thirty-five (58.7%) tumourswere aneuploid. High S-phase fraction and aneuploidy were associated with tumours with higher grade of differentiation, greatersize and negative hormonal receptors. In univariate analysis, all the clinicopathological and cytometric features (including patients <40 years and a subgroup presenting hipertetraploid/multiploid tumours), but S-phase fraction and estrogen receptors for disease freesurvival, significantly correlated with clinical outcome. In multivariate analysis, advanced disease stage, DNA aneuploidy and lack ofprogesterone receptors retained statistically significant association with shorter survival. In the subgroup of patients with intermediatedifferentiation tumours (G2), aneuploidy associated with worse prognosis. In the subset of node-negative patients, only estrogen receptorsshowed significant correlation with disease evolution. In node-positive patients, greater size tumours and aneuploidy (in relation tooverall survival) were indicators of worse prognosis.Conclusion: Along with disease staging and hormone-receptor expression, DNA ploidy is an independent prognostic biomarker oflong-term survival in breast invasive ductal carcinoma.


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