Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma

A E Pinto¹, S André¹, T Pereira¹, S Nóbrega², J Soares¹

¹ Departamento de Patologia Morfológica, Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Francisco Gentil, Centro de Lisboa, 1099–023 Lisboa Codex, Portugal
² Registo Oncológico Regional (ROR-Sul), Instituto Português de Oncologia de Francisco Gentil

Correspondence to:
Dr Pinto

Aims—To investigate the prognostic value of recently proposed flow cytometric S-phase fraction (SPF) variables (average SPF and SPF tertiles) compared with conventional SPF, and to compare the one with the best predictive value with the immunohistochemical Ki-67 index in breast carcinoma.

Methods—A short term follow up study (median, 39.6 months) of a large series of patients (n = 306) was conducted. DNA ploidy was analysed on fresh/frozen tumour samples by flow cytometry, and the SPF was calculated from the DNA histogram using an algorithm. The Ki-67 index was assessed on paraffin wax embedded material by immunohistochemistry (cut off point, 10%). The two methods were compared by means of statistics, and the prognostic significance of both in relation to disease free survival (DFS) and overall survival (OS) was determined.

Results—SPF and Ki-67 analysis was performed on 234 (76.5%) and 295 (96.4%) tumours, respectively. The two assessments were simultaneously available in 230 cases. All SPF variables analysed in the whole series significantly correlated with disease evolution, with the conventional median SPF (cut off point, 6.1%) showing the highest predictive value in relation to both DFS (p = 0.0001) and OS (p = 0.0003). SPF tertiles and median SPF evaluated according to DNA ploidy status had no prognostic significance. The Ki-67 index showed a trend in relation to DFS (p = 0.086) that did not reach significance, and no correlation with OS was found (p = 0.264). The comparative analysis of SPF and Ki-67 revealed some agreement between the two methods (agreement, 69.13%; statistic, 0.3844; p < 0.001), especially in the subgroup of diploid tumours.

Conclusions—Flow cytometric SPF is a better prognosticator than the Ki-67 index, but only SPF variables applied in the whole series show potential clinical usefulness.

Key Words: breast carcinoma • DNA flow cytometry • immunohistochemistry • S-phase fraction • Ki-67 • prognosis

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