title: High tPA-expression in primary melanoma of the limb correlates with good prognosis.
abstract: To investigate whether the course of primary melanoma disease correlates with expression of the various components of the proteolytic plasminogen activation (PA) system, immunohistochemical stainings for activators of plasminogen (tissue type (tPA) and urokinase type (uPA)), inhibitors of plasminogen activation (type 1 (PAI-1) and type 2 (PAI-2)) and the receptor for uPA (uPAR) were performed on 214 routinely processed melanoma lesions. All lesions were primary cutaneous melanomas, minimally 1.5 mm thick, and derived from patients with only local disease at the moment of diagnosis (clinically stage II (T(3-4)N(0)M(0)), American Joint Committee on Cancer). Median patient follow-up was 6.1 years. Single variables as immunohistochemical staining results (extent of tumour cell staining, pattern of tumour cell staining and for some components also staining of stromal cells), histopathological and clinical parameters as well as treatment variables were analysed in order to assess their prognostic importance, in terms of time to recurrence, time to distant metastasis and duration of survival. The extent of tPA tumour cell positivity, categorized as 0-5%, 6-50% and 51-100%, appeared to be of importance for these end-points. Lesions with 51-100% tPA-positive tumour cells were found to have the best prognosis, whereas lesions with 6-50% tPA-positive tumour cells had the worst. Moreover, the prognostic significance of Breslow thickness, microscopic ulceration and sex was confirmed in this study. Multivariate analyses, incorporating these relevant factors, showed that the extent of tPA tumour cell positivity was an independent prognostic factor for distant metastasis-free interval (P = 0.012) and for the duration of survival (P = 0.043).
authors.affiliation: Department of Pathology, Department of Epidemiology, University Medical Center St. Radboud, PO Box 9101, Nijmegen, HB, 6500, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Ferrier
authors.forename: S
authors.initials: S
authors.lastname: Suciu
authors.forename: W L
authors.initials: WL
authors.lastname: van Geloof
authors.forename: H
authors.initials: H
authors.lastname: Straatman
authors.forename: A M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: H S
authors.initials: HS
authors.lastname: Koops
authors.forename: B B
authors.initials: BB
authors.lastname: Kroon
authors.forename: F J
authors.initials: FJ
authors.lastname: Lejeune
authors.forename: U R
authors.initials: UR
authors.lastname: Kleeberg
authors.forename: G N
authors.initials: GN
authors.lastname: van Muijen
authors.forename: D J
authors.initials: DJ
authors.lastname: Ruiter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005121:Extremities; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator