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Etiopathogenesis
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Dario Didona, Biagio Didona, Giovanni Paolino, Raffaele Dante Caposiena Caro
Both peripheral nerve sheath and melanocytes arise from neural crest cells (NCC). These cells migrate from the neural tube to dorsolateral and ventral directions [38] (Figure 5.5). On the one hand, cells with only a dorsolateral trajectory are committed to melanocytic fate; on the other hand, cells with a ventral trajectory are committed to neuronal, glial/melanocyte, or endoneurial fibroblast fate [38]. It has been shown that SOX10+ NCCs fail to initiate the neuronogenesis, adopting a glial pathway to give rise to Schwann cells and melanocytes, highlighting the link between pigmentary disorders (as vitiligo) and neural cells [38]. Neuregulin 1 is an axon-derived growth factor which, when overexpressed, promotes glial fate and suppresses melanocytic activity [39]. Furthermore, melanocytes with the overexpression of embryo retinal epithelium can dedifferentiate back to their unpigmented glial progenitor [39].
Skin cancer
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Microscopically, the tumour is composed of melanocytes that invade along the superficial layers of the skin and penetrate the basement membrane into the deeper layers of the dermis. The cells characteristically stain for S100, melan A and HMB45 reflecting their origin from neural crest cells. Diagnosis may be confirmed with positivity for MiTF1 and SOX10. A lymphocytic infiltrate is common, reflecting a host cellular immune response.
Waardenburg syndrome
Published in Electra Nicolaidou, Clio Dessinioti, Andreas D. Katsambas, Hypopigmentation, 2019
Carmen Maria Salavastru, Stefana Cretu, George Sorin Tiplica
SOX10 is a transcription factor responsible for the development and preservation of melanocytes, Schwann cells, and enteric ganglion cells, all of which derive from the neural crest cells.17 The gene is expressed in the developing embryo in neural crest cells that contribute to the formation of the peripheral nervous system and transiently in melanoblasts. In later stages of development, it is also expressed in the central nervous system, reaching a maximum level of expression at this site in the adult life. Among the transcription factors modulated by SOX10 are PAX3 and MITF.13 Individuals with WS and SOX10 mutations are heterozygotes. In the homozygous state, SOX10 mutations are lethal in early infancy or in utero.10
The significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the development of terminally differentiated Schwann cells in vitro
Published in International Journal of Neuroscience, 2021
Xizhong Yang, Cuijie Ji, Xinyue Liu, Chaoqun Zheng, Yanxin Zhang, Ruowu Shen, Zangong Zhou
Neuregulin-1 (NRG-1) is a member of the family of regulatory proteins that contain the EGF (epidermal growth factor)-like domain. It is a type of transmembrane protein that regulates the growth and development of glial cells and neurons [8]. The functional receptor of NRG is the ErbB receptor, which includes ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4. ErbB is a member of the EGF receptor family of transmembrane tyrosine kinases. Both ErbB2 and ErbB3 receptors are required in the development of SCs, but these two receptors have different effects; ErbB3 can bind with extracellular ligands with high affinity even though it is inactive, while ErbB2 tyrosine kinase activity can activate downstream signaling [9]. Sox10 belongs to the Sox family, members of which contain a DNA binding domain that is similar to the HMG (high mobility group) domain of the SRY transcription factor family [10]. The structure of Sox10 is highly conserved, especially the structure of its functional domains, such as the N-terminal to C-terminal dimerization domain, the HMG domain, and the protein interaction (K2) domain [11]. The Sox gene family is involved in stem cell maintenance, cell differentiation and tissue formation. Sox10 plays an important role in the formation of the neural crest and peripheral nervous system, the maturation and terminal differentiation of SCs, and the differentiation of melanocytes. Sox10 and Oct6 have synergistic effects on the differentiation and development of SCs [12]. In addition, in the central nervous system and the peripheral nervous system, Sox10 is highly expressed in neural crest cells and glial cells.
Frequency of metastasis to the gastrointestinal tract determined by endoscopy in a community-based gastroenterology practice
Published in Baylor University Medical Center Proceedings, 2021
Vishal Kaila, Rajeev Jain, Donna J. Lager, Pamela Jensen, Mark Feldman
The biopsies obtained at the time of endoscopy were fixed in formalin and processed routinely; hematoxylin/eosin–stained tissue sections were prepared. Slides were then examined and diagnoses rendered by board-certified pathologists from ProPath, who were located at Texas Digestive Disease Consultants, or by pathologists in the Department of Pathology at Texas Health Presbyterian Hospital Dallas. Additional immunohistochemical stains were used to help establish the origin of the metastatic tumors. CDX2 is a highly sensitive and specific marker for adenocarcinomas of intestinal origin.6 Thyroid transcription factor-1, expressed in the epithelial cells of the thyroid gland and lung, was used to identify lung adenocarcinomas.7 Though both lung and breast adenocarcinomas can express estrogen receptor and HER2, other markers such as GATA3 were utilized to distinguish breast adenocarcinomas from other malignancies.8 A immunohistochemical profile that was positive for CK7 and negative for CK20 and CDX2 supported an ovarian origin of the metastasis.9 Prostate-specific antigen stains were used to classify prostate adenocarcinomas.10 PAX8 is frequently positive with metastatic tumors of renal origin.11 SOX10 and Mart 1 immunohistochemistry stains are helpful to confirm the diagnosis of melanoma.12
Close proximity of immune and tumor cells underlies response to anti-PD-1 based therapies in metastatic melanoma patients
Published in OncoImmunology, 2020
Tuba N. Gide, Ines P. Silva, Camelia Quek, Tasnia Ahmed, Alexander M. Menzies, Matteo S. Carlino, Robyn P.M. Saw, John F. Thompson, Marcel Batten, Georgina V. Long, Richard A. Scolyer, James S. Wilmott
Furthermore, our study utilized SOX10 as a melanoma marker to calculate the spatial distances of the immune cell populations to melanoma cells. While the melanoma cells in our study were all homogenously positive for SOX10, it has been shown that de-differentiation in melanomas is linked to loss of SOX10 during treatment with small molecule BRAF inhibitors28 and de-differentiation has been associated with immunotherapy resistance.29 Therefore, heterogeneous melanoma expression of SOX10 should be considered when applying the techniques outlined in this study, particularly during treatment with targeted or immunotherapies.