Divergent Cellular Differentiation Pathways during the Invasive Stage of Cutaneous Malignant Melanoma Progression
| Autor: | Bridget Finnerty, Jon A. Reed, Anthony P. Albino |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pathology
medicine.medical_specialty Skin Neoplasms Cellular differentiation Schwann cell Receptors Nerve Growth Factor Biology medicine.disease_cause Receptor Nerve Growth Factor Pathology and Forensic Medicine GAP-43 Protein Biomarkers Tumor medicine Humans Nevus skin and connective tissue diseases Melanoma Cell Differentiation Melanocytic nevus medicine.disease Immunohistochemistry CD56 Antigen medicine.anatomical_structure Disease Progression Neural cell adhesion molecule Schwann Cells Carcinogenesis Regular Articles Signal Transduction |
| Zdroj: | The American Journal of Pathology. 155:549-555 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)65150-4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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