Innominato P F, Libbrecht L, van den Oord J J
Department of Pathology, Laboratory of Morphology and Molecular Pathology, University Hospitals, Katholieke Universiteit Leuven, Minderbroedersstraat 12, B-3000 Leuven, Belgium.
J Pathol. 2001 May;194(1):95-100. doi: 10.1002/path.861.
The neurotrophins (NTs) are a group of growth factors involved in the development of the nervous system and presumed to play a role in neural crest-derived tumours. The expression of three NTs (NGF, BDNF, and NT-3) and their receptors (NTRs; i.e. low-affinity pan-NT receptor p75, Trk-B, and Trk-C) was studied in frozen sections of benign and malignant cutaneous pigment cell lesions, using immunohistochemistry. In order to understand the possible role of these growth factors and their receptors in the progression of primary cutaneous malignant melanomas (PCMMs), their distribution in the radial (RGP) and vertical (VGP) growth phases was particularly studied. While most of the common acquired naevi were unreactive, Spitz and blue naevi showed scattered immunoreactive cells, especially for the p75 NTR. Dysplastic naevi, but not common naevi, expressed NT-3 in their junctional component. PCMM and melanoma metastases often showed a diffuse pattern of immunostaining. NT-3 was significantly more frequently expressed in the RGP of PCMMs than in the junctional component of benign naevi, whereas more extensive immunoreactivity for NGF was found in the VGP of PCMMs, compared with the RGP; metastases more frequently expressed NGF, BDNF, and Trk-B than PCMMs. Interestingly, neurotropic melanoma expressed all NTs/NTRs except Trk-B. These immuunohistochemical data confirm suggestions from previous in vitro studies that autocrine loops of certain NTs and their respective receptors may be involved in melanoma progression; in addition, NT-3 may be involved in the junctional growth of dysplastic naevi. The precise role of these growth factors in melanoma, however, will await further functional studies.
神经营养因子（NTs）是一组参与神经系统发育的生长因子，据推测在神经嵴衍生肿瘤中发挥作用。利用免疫组织化学方法，研究了三种NTs（神经生长因子[NGF]、脑源性神经营养因子[BDNF]和神经营养因子-3[NT-3]）及其受体（神经营养因子受体[NTRs]；即低亲和力泛NTs受体p75、酪氨酸激酶受体B[Trk-B]和酪氨酸激酶受体C[Trk-C]）在良性和恶性皮肤色素细胞病变冰冻切片中的表达。为了解这些生长因子及其受体在原发性皮肤恶性黑色素瘤（PCMMs）进展中的可能作用，特别研究了它们在放射状（RGP）和垂直状（VGP）生长阶段的分布。虽然大多数常见的后天性痣无反应，但Spitz痣和蓝痣显示有散在的免疫反应性细胞，尤其是p75 NTR。发育异常痣而非普通痣在其交界成分中表达NT-3。PCMM和黑色素瘤转移灶常显示弥漫性免疫染色模式。NT-3在PCMMs的RGP中表达明显比在良性痣的交界成分中更频繁，而与RGP相比，在PCMMs的VGP中发现NGF有更广泛的免疫反应性；转移灶比PCMMs更频繁地表达NGF、BDNF和Trk-B。有趣的是，嗜神经性黑色素瘤表达除Trk-B外的所有NTs/NTRs。这些免疫组织化学数据证实了先前体外研究的推测，即某些NTs及其各自受体的自分泌环可能参与黑色素瘤进展；此外，NT-3可能参与发育异常痣的交界性生长。然而，这些生长因子在黑色素瘤中的确切作用还有待进一步的功能研究。
