Improving the prognostic value of DNA flow cytometry in metastatic melanoma by combining ploidy and S-phase fraction.

The prognostic value of cellular DNA content of melanoma metastases was investigated in tumours from 114 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. Thirty-six percent of the tumours were diploid and 64% aneuploid. For 91 patients the S-phase fraction was calculable. Tumour ploidy and S-phase fraction (SPF) were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Patients with either aneuploid or low SPF tumours survived longer than did those with diploid or high SPF tumours. By combining DNA ploidy and SPF, three types of DNA histograms could be defined, associated with favourable, intermediate and poor prognosis. Patients with aneuploid, low SPF metastases showed a median survival of 57 months, whereas the high-risk group with diploid, high SPF metastases survived only 13 months. When ploidy, SPF, age, sex, TNM stage and duration of disease-free survival were analysed as covariates the division of flow cytometry histograms into these three types resulted in the most significant prognostic factor (p < 0.001) in the Cox multivariate analysis.