DNA ploidy, proliferation markers and prognosis in malignant melanoma

• Malignant melanoma is a serious disease when metastases occur. It is therefore important to investigate possible tools for prediction to the outcome of the disease. In the present investigation 265 patients with cutaneous malignant melanoma and uveal melanoma was investigated with flow cytometry.In 82 patients with stage Ill cutaneous melanoma we found that the DNA ploidy and S-phase fraction on the primacy tumours and the time to the first metastases predicted the post-recurrence survival. Patients with diploid melanoma cells, low S-phase fraction and a long recurrence free interval had a rather favourable prognosis despite presence of regional metastases. In 55 subjects a significantly higher frequency of aneuploidy was found in metastases compared to the primary tumour of the same patients, suggesting a higher growth potential in metastases.A high S-phase fraction measured on the last histologically metastases before chemotherapy treatment was associated with an objective response and a longer survival in 87 patients with disseminated melanoma. The anatomical location of the metastases also predicted objective response, and together with a high S-phase fraction, a large number of metastatic sites and objective response were associated with survival.DNA ploidy together with histopathologic type and tumour size could predict the survival in 96 patients with uveal melanoma. A small, diploid tumour of spindle-cell type gave a significantly longer survival than a large, aneuploid tumour of epithelioid-cell type. In univariate statistical analysis the S-phase fraction predicted survival, but did not remain as a prognostic factor after adjustments for ploidy, histologic type and tumoursize. DNA ploidy and S-phase fraction were correlated with well-known histopathologic features. The proliferation marker Ki-67 was correlated with well-known histopathological features and associated with survival in 79 patients. This was not the case with the proliferation marker PCNA. Patients with uveal melanomas containing a high percentage of Ki-67 positive nuclei had a significant shorter survival than those with a low percentage.

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