Ferrier C M, Suciu S, van Geloof W L, Straatman H, Eggermont A M, Koops H S, Kroon B B, Lejeune F J, Kleeberg U R, van Muijen G N, Ruiter D J
Department of Pathology, Department of Epidemiology, University Medical Center St. Radboud, PO Box 9101, Nijmegen, HB, 6500, The Netherlands.
Br J Cancer. 2000 Nov;83(10):1351-9. doi: 10.1054/bjoc.2000.1460.
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).
为了研究原发性黑色素瘤病程是否与蛋白水解性纤溶酶原激活（PA）系统各组分的表达相关，对214例常规处理的黑色素瘤病灶进行了纤溶酶原激活剂（组织型（tPA）和尿激酶型（uPA））、纤溶酶原激活抑制剂（1型（PAI-1）和2型（PAI-2））以及uPA受体（uPAR）的免疫组织化学染色。所有病灶均为原发性皮肤黑色素瘤，厚度至少1.5 mm，来源于诊断时仅患有局部疾病的患者（美国癌症联合委员会临床分期II期（T(3 - 4)N(0)M(0)））。患者中位随访时间为6.1年。分析了作为免疫组织化学染色结果的单变量（肿瘤细胞染色范围、肿瘤细胞染色模式以及某些组分的基质细胞染色情况）、组织病理学和临床参数以及治疗变量，以便从复发时间、远处转移时间和生存时长方面评估它们的预后重要性。tPA肿瘤细胞阳性程度分为0 - 5%、6 - 50%和%51 - 100%，对于这些终点似乎具有重要意义。发现tPA阳性肿瘤细胞比例为51 - 100%的病灶预后最佳，而tPA阳性肿瘤细胞比例为6 - 50%的病灶预后最差。此外，本研究证实了Breslow厚度、显微镜下溃疡和性别的预后意义。纳入这些相关因素的多变量分析表明，tPA肿瘤细胞阳性程度是无远处转移间期（P = 0.012）和生存时长（P = 0.043）的独立预后因素。
