Ferrier Cilia M, Van Geloof Winny L, Straatman Huub, Van De Molengraft Fred J J M, Van Muijen Goos N P, Ruiter Dirk J
Department of Pathology, University Medical Centre St Radboud, Nijmegen, The Netherlands.
J Pathol. 2002 Sep;198(1):92-9. doi: 10.1002/path.1167.
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.
纤溶酶原激活(PA)系统参与侵袭和转移过程。其主要成分包括尿激酶(uPA)和组织型纤溶酶原激活剂(tPA)、1型和2型纤溶酶原激活抑制剂(PAI - 1和PAI - 2)以及尿激酶受体(uPAR)。在本研究中,一方面比较了Spitz痣中纤溶酶原激活成分的表达与普通痣和发育异常痣中的表达,另一方面比较了与原发性皮肤黑色素瘤中的表达。Spitz痣中,uPA的黑素细胞阳性率为0%(0/36),tPA为30%(6/20),PAI - 1为10%(3/35),PAI - 2为40%(8/21),uPAR为60%(13/21)。这远远超过了在普通痣(n = 25)和发育异常痣(n = 15)中发现的表达情况,普通痣和发育异常痣仅显示PAI - 2的黑素细胞阳性(分别为20%和15%),且在1例发育异常痣中还显示uPAR阳性。这比原发性黑色素瘤肿瘤细胞阳性的比例要低得多(对于大多数成分而言有显著差异),原发性黑色素瘤中uPA的阳性比例为30%(11/38),tPA为80%(19/24),PAI - 1为75%(28/38),PAI - 2为80%(19/24),uPAR为80%(19/24)。本研究的主要发现是,首先,Spitz痣可能表达纤溶酶原激活剂(tPA)、抑制剂和PA系统的受体,但比例远低于皮肤黑色素瘤;其次,Spitz痣不表达尿激酶,而一些黑色素瘤表达。因此,uPA阳性可能提示黑色素瘤。然而,染色结果的重叠表明PA系统在Spitz痣和原发性黑色素瘤的鉴别诊断中价值有限。由于Spitz痣表达丝氨酸蛋白酶成分,其可能利用这种蛋白水解机制来完成基质降解,尽管其方式比黑色素瘤更受限制,可能是短暂的。