Melanocyte differentiation

The neural crest cells are the pluripotent parent cells of a number of different cell lineages, including 

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Tobin DJ, Foitzik K, Reinheckel T, Mecklenburg L, Botchkarev VA, et al. The lysosomal protease cathepsin L is an important regulator of keratinocyte and melanocyte differentiation during hair follicle morphogenesis and cycling. Am. J. Pathol. 2002 160 1807-1821. 

One true exception to the last statement is represented by the ability of MART-l/melan-A (but not HMB-45, NKI-beteb, or HMB-50) to label the tumor cells of a subset of adrenocortical carcinomas and sex-cord tumors of the gonads (Fig. 7.13). " 4° No evidence of true melanocytic differentiation has been seen in such neoplasms, and MART-1 antibodies are presumably recognizing an antigenic epitope in those steroidogenic proliferations, which is shared with the gplOO/PMel 17 molecules. 

In normal melaninogenesis, the amino acid tyrosine is hydroxylated to form 3,4-dihydroxyphenylalanine ( dopa ), which is then oxidized to dopa-quinone. The latter moiety is polymerized to form melanin, thereafter combining with melanoprotein to form a stable complex within premelanosomes and melanosomes. Tyrosinase plays a central role in this process, by catalyzing the first step in the stated sequence. As such, it is a specific marker for melanocytic differentiation. This premise has been affirmed by studies showing that tyrosinase gene transcripts are strictly confined to melanin-producing cells. 

FIGURE 7.15 "Melanotic" schwannoma, in which a high proportion of the tumor cells demonstrate divergent melanocytic differentiation. 

Busam KJ, Jungbluth AA. Melan-A, a new melanocytic differentiation marker. Adv Anat Pathol. 1999 6 12-18. 

Orchard GE. Comparison of immunohistochemical labeling of melanocyte differentiation antibodies melan-A, tyrosinase, and HMB-45 with NKI/C3 and SlOO protein in the evaluation of benign nevi and malignant melanoma. Histochem J. 2000 32 475-481. 

Busam KJ, Kucukgol D, Sato E, et al. Immunohistochemical analysis of novel monoclonal antibody PNL2 and comparison with other melanocyte differentiation markers. Am ] Surg Pathol. 2005 29 400-406. 

Lohmarm GM, Hwu WJ, Iversen K, et al. Primary malignant melanoma of the oesophagus a clinical and pathological study with emphasis on the immunophenotype of the tumours for melanocyte differentiation markers and cancer/testis antigens. Melanoma Res. 2003 13 595-601. 

Melan A Malan A is a protein encoded by the MART-1 gene. Melan A is expressed in melanin producing cells and considered as a specific melanocyte differentiation and melanoma marker. 

Melanoma can be diagnosed throngh the monitoring of tyrosinase, a cytoplasmic melanocyte differentiation protein, which is a key enzyme in melanin synthesis and has been listed as important melanoma biomarker. Mossberg et al. (2014) developed an electrochemical biosensor platform with an amperometric detection mode to detect the enzymatic activity of tyrosinase in fresh biopsy samples withont pretreatment of the samples. The combination of this method with modem portable devices can provide interesting POC sensors in the fnture. 

DeLuca, M., Franzi, A., D Anna, E, Zicca, A., Albanese, E., Bondanza, S., and Cancedda, R., Co-culture of human keratinocytes and melanocytes differentiated melanocytes are physiologically organized in the basal layer of the cultured epithelium, Eur. J. Cell Biol, 46, 176, 1988. 

Kinkor Z, Hes O. Pleomorphic epithehoid/clear cell malignant tumor of the uterus exhibiting both myoid and melanocytic differentiation leiomyosarcoma or PEComa A case report and a review of the Uterature. Cesk Patol 2007 43(3) 103-108. 

Jager E, Ringhofier M, Karbach J, Arand M, Oesch F, Knuth A. Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses evidence for immunoselection of antigen-loss variants in vivo. Int J Cancer 1996 66 470 76. 

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