title: Spitz naevi may express components of the plasminogen activation system.
abstract: The plasminogen activation (PA) system is involved in the process of invasion and metastasis. Its major components are urokinase (uPA) and tissue-type plasminogen activator (tPA), plasminogen activation inhibitor type 1 and 2 (PAI-1 and PAI-2) and a receptor for urokinase (uPAR). In this study, the expression of plasminogen activation components in Spitz naevi was compared with that in common and dysplastic naevi on the one hand and primary cutaneous melanomas on the other. Spitz naevi had melanocytic positivity for uPA in 0% (0/36), tPA in 30% (6/20), PAI-1 in 10% (3/35), PAI-2 in 40% (8/21) and uPAR in 60% (13/21) of cases. This far exceeded the expression found in common (n = 25) and dysplastic (n = 15) naevi, which only showed melanocytic positivity for PAI-2 (20% and 15% respectively) and in one dysplastic naevus also for uPAR. This was much (for most components significantly) less than the proportion of primary melanomas with tumour cell positivity, which was 30% (11/38) for uPA, 80% (19/24) for tPA, 75% (28/38) for PAI-1, 80% (19/24) for PAI-2 and 80% (19/24) for uPAR. The main findings of this study are that Spitz naevi, firstly, may express plasminogen activator (tPA), inhibitors and the receptor of the PA system, but in a much smaller proportion than cutaneous melanomas; and secondly, do not express urokinase, whereas some of the melanomas do. uPA positivity may therefore be suggestive of melanoma. However, overlapping staining results imply that the PA system has limited value in the differential diagnosis between Spitz naevus and primary melanoma. As serine protease components are expressed, Spitz naevi may use this proteolytic machinery to accomplish matrix degradation, although in a more restricted, possibly transient manner than melanomas.
authors.affiliation: Department of Pathology, University Medical Centre St Radboud, Nijmegen, The Netherlands. cilia.ferrier@pathol.azn.nl
authors.forename: Cilia M
authors.initials: CM
authors.lastname: Ferrier
authors.forename: Winny L
authors.initials: WL
authors.lastname: Van Geloof
authors.forename: Huub
authors.initials: H
authors.lastname: Straatman
authors.forename: Fred J J M
authors.initials: FJ
authors.lastname: Van De Molengraft
authors.forename: Goos N P
authors.initials: GN
authors.lastname: Van Muijen
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Ruiter
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D003937:Diagnosis, Differential; D004416:Dysplastic Nevus Syndrome / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D018332:Nevus, Epithelioid and Spindle Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D010960:Plasminogen Activators / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C524898:PLAUR protein, human; D015849:Plasminogen Inactivators; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D015842:Serine Proteinase Inhibitors; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator