Ratio of some fibrinolytic system components and biological aggressiveness of melanoma.

Abstract

e21069 Background: Melanomas of early stages in a horizontal growth phase can masquerade as a melanocytic nevus or other benign skin lesions. Activation of plasmin/plasminogen system is typical of both physiologic and pathologic processes. Cell remodeling and neoangiogenesis play critical role in melanoma invasion and metastasis. The purpose of the study was comparative analysis of plasmin/plasminogen system in tissues of nevi and melanomas of different sizes and extension. Methods: Activity of plasmin and plasminogen was studied and antigen and activity assays (ELISA) were performed for uPA, tPA and PAI-1 in tissues of nevi (n = 30) and melanomas pТ1-2N0M0 (n = 17) and pТ3-4N0-1M0 (n = 23). Intact tissue (n = 15) obtained in surgical treatment of patients without cancer was used for the control. Results: Plasminogen levels were decreased by 2 times in tissues of nevi and pТ1-2N0M0 melanoma, while plasmin was unchanged. pТ1-2N0M0 melanoma significantly differed from nevi by a marked activation of uPA without PAI-1 increase. Activation of plasminogen system in both рТ1-2N0M0 melanoma and in nevi was not accompanied by plasmin accumulation. The main difference between tissues of nevi and pТ1-2N0M0 melanoma was the uPA/PAI-1 ratio reduction by more than 40 times in nevi. pТ3-4N0-1M0 melanoma was characterized by plasmin level increase by more than 19 times and uPA activity and content increase by 2.5 times, compared to pТ1-2N0M0, without an increase in PAI-1 activity. The uPA/PAI-1 ratio almost doubled. Conclusions: Normal plasmin levels in nevi and melanomas in a horizontal growth phase are probably the result of its inhibitors activity. Increased activity of fibrinolytic system, plasmin accumulation and uPA/PAI-1 increase in a vertical growth phase determine proliferative, invasive and metastatic potential of tumors.