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Divergent Cellular Differentiation Pathways during the Invasive Stage of Cutaneous Malignant Melanoma Progression

机译:皮肤恶性黑色素瘤进展期侵袭阶段的不同细胞分化途径

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摘要

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 (2 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学特征 。这些与分化相关的变化通常 在黑素瘤中未观察到。但是,痣细胞不能完全 概括雪旺细胞表型,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 nevi和恶性黑色素瘤中低亲和力神经生长因子受体 (p75NGFR),神经细胞的表达。粘附分子(CD56 / N-CAM)和与生长相关的 磷酸蛋白43(GAP-43)。这三种蛋白定义了 雪旺细胞发育的最早阶段,但在髓鞘雪旺细胞或正常黑素细胞中不表达。 p75NGFR在25的25(100%)中表达 ,在25(92%)的23 23(sup> 中表达CD56 / N-CAM和GAP-43,主要在C型痣中表达细胞和痣 小体。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,这三种蛋白质各自的 的表达仅限于”( 2 P <0.0001)。无 的黑素瘤表达了所有三种蛋白质(ANOVA P <0.0001)。 这些数据证实并扩展了早期研究,显示了真皮中黑素细胞的末端 分化可以概括一些 在雪旺氏细胞发展的早期阶段观察到的情况 ,并且浸润性黑素瘤遵循不同的途径,研究 这些早期分化事件可能有助于识别特定的 > 在相关的信号传导途径中的缺陷,并为长期黑色素瘤的治疗建立了稳定的 靶标。

著录项

  • 来源
    《American Journal of Pathology》 |1999年第2期|549-555|共7页
  • 作者单位

    From the Section of Dermatopathology,Department of Pathology, Baylor College of Medicine, Houston, Texas;

    the Dermatopathology Division,Department of Pathology, New York Presbyterian Hospital-Cornell Medical Center, New York, New York;

    and The American Health Foundation,Valhalla, New York;

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