Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome

The present study analysed by immunohistochemistry the protein level of cyc lin A and Ki-67 in a panel of paraffin-embedded tissue obtained from 172 pr imary (110 superficial and 62 nodular) and 73 metastatic melanomas, and ten benign naevi. Since cyclin A exists in the same quaternary complex in the S-phase of the cell cycle as the cdk inhibitor p21(WAF1/CIP1), the levels o f the two proteins were compared. Cyclin A and Ki-67 were heterogeneously e xpressed in the malignant tumours, whereas in benign naevi, only rare posit ive cells were detected. In superficial spreading melanomas, the cyclin A l evel was related to tumour thickness, with less expression in thinner lesio ns (p < 0.00001), and to Ki-67 (p < 0.00001) and p2(WAF1/CIP1) (p = 0.01) s cores. Multivariate analysis showed that in addition to the depth of the pr imary tumour, the protein level of cyclin A was an independent indicator of relapse-free period (thickness, p < 0.00001; cyclin A, p = 0.0003). In con trast, in nodular melanoma, the cyclin A level was associated with Ki-67 ex pression, but neither cyclin A nor Ki-67 was related to tumour thickness (c yclin A, p = 0.06; Ki-67, p = 0.61) and neither had any impact on relapse-f ree (cyclin A, p = 0.64, Ki-67, p = 0.32) or overall (cyclin A, p = 0.94; K i-67, p = 0.45) survival. In conclusion, the results indicate that cyclin A is a strong prognostic factor for patients with superficial spreading mela nomas. In nodular melanomas, the proliferation rate seems to have little im pact on disease progression. Copyright (C) 2001 John Wiley & Sons, Ltd.