Melanocytic nevus cells in the dermis adopt many morphological features of Schwann cells. These differentiation-related changes typically are not observed in melanomas. However, nevus cells do not fully recapitulate a Schwann cell phenotype, because they lack expression of mature myelin-associated proteins. In this study, melanocytic nevi and malignant melanomas were examined by immunohistochemistry for expression of low-affinity nerve growth factor receptor (p75NGFR), neural cell adhesion molecule (CD56/N-CAM), and growth-associated phosphoprotein-43 (GAP-43). These three proteins define the earliest stages of Schwann cell development but are not expressed in myelinated Schwann cells or normal melanocytes. p75NGFR was expressed in 25 of 25 (100%) and CD56/N-CAM and GAP-43 in 23 of 25 (92%) nevi, predominantly in type C nevus cells and nevic corpuscles. Most (84%) of the nevi expressed all three proteins. In primary invasive and metastatic melanoma, expression of each of the three proteins was limited to ≤20% of lesions but was not observed in any melanoma in situ (χ2 P < 0.0001). None of the melanomas expressed all three proteins (ANOVA P < 0.0001). These data confirm and extend earlier studies by showing that terminal differentiation of melanocytes in the dermis recapitulates some aspects observed in the earliest stages of Schwann cell development and that invasive melanomas follow a divergent pathway. Studying these early differentiation events may help to identify specific defects in the relevant signaling pathways and establish tenable targets for therapy of advanced-stage melanoma.
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机译:真皮中的黑素细胞痣细胞具有许旺细胞的许多形态特征。这些分化相关的变化通常在黑色素瘤中未观察到。但是,痣细胞不能完全概括雪旺细胞的表型,因为它们缺乏成熟的髓磷脂相关蛋白的表达。在这项研究中,通过免疫组织化学检查了黑素细胞痣和恶性黑色素瘤的低亲和力神经生长因子受体(p75NGFR),神经细胞粘附分子(CD56 / N-CAM)和生长相关的磷蛋白43(GAP-43) )。这三种蛋白质定义了雪旺氏细胞发育的最早阶段,但在髓鞘雪旺氏细胞或正常黑素细胞中不表达。 p75NGFR在25个痣中的25个(100%)中表达,CD56 / N-CAM和GAP-43在25个痣中的23个(92%)中表达,主要在C型痣细胞和痣小体中表达。痣中的大多数(84%)表达了所有三种蛋白质。在原发性侵袭性和转移性黑色素瘤中,这三种蛋白的每种表达仅限于≤20%的病灶,但在任何原位黑色素瘤中均未观察到(χ 2 sup> P <0.0001)。黑色素瘤均未表达全部三种蛋白质(ANOVA P <0.0001)。这些数据通过显示真皮中黑素细胞的终末分化概括了在雪旺氏细胞发展的最早阶段中观察到的某些方面,并且侵袭性黑素瘤遵循了不同的途径,从而证实并扩展了先前的研究。研究这些早期分化事件可能有助于鉴定相关信号通路中的特定缺陷,并为晚期黑色素瘤的治疗建立可靠的靶标。
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