PROTEIN EXPRESSION OF THE CELL-CYCLE INHIBITOR P27(KIP1) IN MALIGNANT-MELANOMA - INVERSE CORRELATION WITH DISEASE-FREE SURVIVAL

in the present study we analyzed, by immunohistochemistry, a panel of human melanomas for protein expression of the cyclin-dependent kinase (cdk) inhibitor p27(Kip1) evaluated whether deregulated expression cor relates with clinical outcome for this type of cancer. We found that p 27(Kip1) was strongly expressed by normal melanocytes and benign nevi, whereas in malignant melanoma, a heterogeneous expression pattern was observed. In the case of nodular melanomas the level of p27(Kip1) was found to correlate significantly with the thickness of the tumor, wit h less protein expressed in thicker lesions. We also found that patien ts having tumors with fewer than 5% p27(Kip1)-staining cells had a sig nificantly higher risk of early relapse of their disease compared with those expressing moderate or high levels. In contrast, the level of p 27(Kip1) did not correlate with tumor thickness or disease-free surviv al in patients with superficial spreading melanomas, suggesting that p 27(Kip1) may play different roles in these two major pathological subg roups of malignant melanoma. Furthermore, p27(Kip1) did not appear to have an influence on overall survival for either subgroup. When we exa mined the combined effect of p21(WAF1/CIP1) (another cdk inhibitor) an d p27(Kip1) On clinical outcome, we found that analysis of these two c dk inhibitors together may have greater prognostic potential than eith er alone. In conclusion, our results suggest that virtually complete l oss of p27(Kip1) protein expression has potential importance as a prog nostic indicator of early relapse in patients with nodular melanoma, T he results, furthermore, underscore the value of analyzing multiple ce ll cycle regulatory proteins to obtain the most reliable indication of prognosis.