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Melanocytic Cells (melanocytic + cell)
Selected AbstractsCombined malignant melanoma and basal cell carcinoma tumor of the intermingled typeJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2007Markus Braun-Falco Background:, The combination of malignant melanoma (MM) and basal cell carcinoma (BCC) within a single tumor is an unusual finding. Case report:, An 84-year-old white man with a pigmented tumor on the back showing a combination of MM and BCC. Results:, A 1.5 × 1.5-cm irregular brown lesion on the back was clinically suggestive of MM. Histopathologically, the lesions turned out to be a combined tumor consisting of a superficial BCC and a regressive MM with a tumor thickness of 1.25 mm. The conglomerates of the BCC lay within the MM and were admixed with a high number of Melan-A-positive melanocytic cells. Conclusion:, By reviewing the low number of published cases, we found that a combined MM-BCC tumor exists in two variants: a collision type in which components of each cell type are clearly demarcated and an intermingled type in which both cell types grow intimately together. Although both types occur as a mere incidence, in particular, the intermingled type may be diagnostically challenging and the evaluation of its dignity may be questionable. [source] Cadherin expression pattern in melanocytic tumors more likely depends on the melanocyte environment than on tumor cell progressionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Sven Krengel Background:, Adhesion molecules have been assigned an important role in melanocytic tumor progression. By the loss of E-cadherin, melanocytes might escape the control of neighbouring keratinocytes. Although in vitro data support this hypothesis, there are yet no conclusive immunohistochemical results on cadherin expression in melanocytic tumors. Objective:, To gain detailed insight in the expression of cadherins and their cytoplasmic binding partners, the catenins, in various types of benign and malignant melanocytic neoplasms. Methods:, Immunohistochemical analysis of the expression of E-, P-, and N-cadherin and ,-, ,-, and ,-catenin in compound and dermal nevi, Spitz nevi, blue nevi, ultraviolet B (UVB)-irradiated nevi, and malignant melanomas of various tumor thickness. Results:, In both nevi and melanomas, E-cadherin expression in melanocytic cells decreased, following a gradient from junctional to deeper dermal localization. The pattern of E-cadherin expression was more heterogeneous in melanomas than in nevi. In some melanomas, E-cadherin was only weakly positive in the epidermal tumor cells. P-cadherin expression was similar to that of E-cadherin. N-cadherin expression in melanocytic lesions was a rare finding, however, a small percentage of melanomas showed expression in some cell nests. Some Spitz nevi exhibited strong N-cadherin immunoreactivity. Most melanocytic cells were ,- and ,-catenin-positive and ,-catenin-negative. UVB irradiation did not influence the expression of cadherins and catenins in melanocytic nevi in vivo. Conclusions:, It is presumed that the gradual loss of E-cadherin expression represents a reaction of melanocytic cells to altered conditions in the dermal environment, e.g. lack of contact to keratinocytes, or new contact with dermal extracellular matrix molecules, respectively. Melanoma cells apparently are less dependent on these environmental factors and, therefore, show a more heterogeneous expression pattern. This might be of importance for the adaptation of the tumor cells to local requirements. However, in view of our results, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven. [source] MMP-2, TIMP-2 and MT1-MMP are differentially expressed in lesional skin of melanocytic nevi and their expression is modulated by UVB-lightJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2002S. Krengel Background:, In malignant melanoma, recent studies have demonstrated an important role of matrix-metalloproteinase 2 (MMP-2), its co-activating enzyme membrane-type matrix-metalloproteinase 1 (MT1-MMP), and the endogenous inhibitor of MMP-2, tissue-inhibitor of matrix metalloproteinase 2 (TIMP-2). Melanocytic nevi are benign neoplasms of the melanocytic lineage, but may exhibit dysplastic features that can be difficult to distinguish from early stage melanoma. As shown in earlier studies, nevi show important morphological and phenotypical changes in response to ultraviolet light (UVB) irradiation. Objective:, To clarify the role of MMP-2, TIMP-2 and MT1-MMP in UVB-irradiated vs. non-irradiated melanocytic nevi. Methods:, Immunohistochemical comparison of the MMP-2, TIMP-2 and MT1-MMP expression pattern. Results:, MMP-2 is expressed by lesional keratinocytes and its expression is up-regulated by UVB-irradiation. MMP-2 expression was not observed in melanocytic cells. TIMP-2, by contrast, is predominantly expressed by melanocytic nevus cells, and its expression is in part down-regulated by UVB-irradiation. MT1-MMP is expressed by basal keratinocytes and to a weaker extent by melanocytic nevus cells. Conclusions:, MMP-2 expression by keratinocytes in nevi probably represents the result of activation of keratinocyte turnover in lesional epidermis. MMP-2 could play a role in the downward movement of junctional nevus cells into the dermis. The reduction of TIMP-2 expression in melanocytic cells by UV-light together with the enhanced expression of MMP-2 in the adjacent epidermis may promote basement membrane degradation. The expression pattern of MT1-MMP in close proximity to epithelial,mesenchymal interfaces underlines the synergistic role of MT1-MMP in this process. [source] Dynamic assembly of chromatin complexes during cellular senescence: implications for the growth arrest of human melanocytic neviAGING CELL, Issue 4 2007Debdutta Bandyopadhyay Summary The retinoblastoma (RB)/p16INK4a pathway regulates senescence of human melanocytes in culture and oncogene-induced senescence of melanocytic nevi in vivo. This senescence response is likely due to chromatin modifications because RB complexes from senescent melanocytes contain increased levels of histone deacetylase (HDAC) activity and tethered HDAC1. Here we show that HDAC1 is prominently detected in p16INK4a -positive, senescent intradermal melanocytic nevi but not in proliferating, recurrent nevus cells that localize to the epidermal/dermal junction. To assess the role of HDAC1 in the senescence of melanocytes and nevi, we used tetracycline-based inducible expression systems in cultured melanocytic cells. We found that HDAC1 drives a sequential and cooperative activity of chromatin remodeling effectors, including transient recruitment of Brahma (Brm1) into RB/HDAC1 mega-complexes, formation of heterochromatin protein 1, (HP1,)/SUV39H1 foci, methylation of H3-K9, stable association of RB with chromatin and significant global heterochromatinization. These chromatin changes coincide with expression of typical markers of senescence, including the senescent-associated ,-galactosidase marker. Notably, formation of RB/HP1, foci and early tethering of RB to chromatin depends on intact Brm1 ATPase activity. As cells reached senescence, ejection of Brm1 from chromatin coincided with its dissociation from HP1,/RB and relocalization to protein complexes of lower molecular weight. These results provide new insights into the role of the RB pathway in regulating cellular senescence and implicate HDAC1 as a likely mediator of early chromatin remodeling events. [source] Large Atypical Melanocytic Nevi in Recessive Dystrophic Epidermolysis Bullosa: Clinicopathological, Ultrastructural, and Dermoscopic StudyPEDIATRIC DERMATOLOGY, Issue 4 2005Fernando Gallardo M.D. The lesion was clinically atypical and fulfilled the criteria for a malignant melanocytic proliferation. A complete surgical excision was performed. Histopathologic examination disclosed a compound melanocytic nevus without melanocytic atypia. Ultrastructural examination showed melanocytic cells located both at the roof and the floor of the blister. Several months later, three pigmentary lesions with a similar clinical appearance developed. Periodic clinical and dermoscopic examinations were recommended. Dermoscopic examination disclosed a globular pattern with brown globules and black dots distributed all over the lesions. The lesions also exhibited blue-greyish dots and multiple rounded white structures corresponding to milia-like cysts. No dermoscopic features suggestive of malignancy were noted. Acquired melanocytic nevi showing atypical clinical features have been reported to occur in areas of blistering in patients with epidermolysis bullosa. These nevi appear as large, asymmetrical pigmentary lesions with irregular borders. Initially, they are very dark in pigmentation, with color variegation and loss of pigment, and even becoming papillomatous over time. Histopathologic examination can show features of compound/junctional nevus as well as persistent/recurrent nevus. The concept of "epidermolysis bullosa nevus" has been proposed to define these peculiar lesions. The clinical, histopathologic and ultrastructural features of these nevi are reviewed. The usefulness of dermoscopic examination in the routine diagnosis and follow-up of these lesions are stressed. [source] ,B-crystallin is mutant B-RAF regulated and contributes to cyclin D1 turnover in melanocytic cellsPIGMENT CELL & MELANOMA RESEARCH, Issue 2 2010Rong Hu Summary The serine/threonine kinase, B-RAF, is frequently mutated in melanoma and is required for cell proliferation. Proteasomal turnover of cyclins and cyclin-dependent kinase inhibitors via E3 ubiquitin ligases regulates cell cycle progression. We previously showed that B-RAF regulates Cks1, a co-factor for the F-box protein Skp2. Recently, a second F-box protein cofactor was identified, ,B-crystallin, that binds Fbx4 and promotes cyclin D1 degradation. Here, we demonstrate that ,B-crystallin is down-regulated in mutant B-RAF melanoma cells compared to melanocytes in a B-RAF and MEK-dependent manner. In a subset of lines, MEK inhibition was sufficient to up-regulate ,B-crystallin protein levels; whereas in other lines combined MEK and proteasome inhibition was required. ,B-crystallin knockdown partially stabilized cyclin D1 in melanocytes. Expression of ,B-crystallin in mutant B-RAF melanoma cells did not promote cyclin D1 turnover under normal conditions, but did enhance turnover following etoposide-induced DNA damage. Together, these data show that ,B-crystallin is highly expressed in melanocytes contributing, in part, to cyclin D1 turnover. Furthermore, ,B-crystallin is down-regulated in a B-RAF-dependent manner in melanoma cells and its re-expression regulates cyclin D1 turnover after DNA damage. [source] The Role of Melanocortin-1 Receptor Polymorphism in Skin Cancer Risk PhenotypesPIGMENT CELL & MELANOMA RESEARCH, Issue 3 2003Richard A. Sturm We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32,140) or weak r (OR = 5; 95% CI 3,11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk. [source] Tissue Factor Expression and Serum Level in Patients with Melanoma does not Correlate with Disease ProgressionPIGMENT CELL & MELANOMA RESEARCH, Issue 3 2001Toshiro Kageshita Not only does tissue factor (TF) play a crucial role in hemostasis and thrombosis, but it is also involved in tumor progression and metastatic potency in some malignant tumors. We evaluated the clinical relevance of TF expression in melanocytic tumors and TF serum level in patients with malignant melanoma. TF expression in benign and malignant melanocytic lesions was examined by immunoperoxidase staining in 20 nevi, 41 primary, and 24 metastatic melanoma lesions. TF was detected in 94, 95, and 100% of these lesions, respectively. The staining pattern was membranous and cytoplasmic both in nevi and melanoma cells. This finding was confirmed by western blot analysis using cultured human melanocytes, nevi cells, and melanoma cell lines. TF was also expressed on blood vessels in benign and malignant melanocytic lesions. Expression of TF in primary melanoma lesions was not associated with any clinicopathological variables. In addition, the serum level of TF was elevated in 14% of patients with melanoma; however, it was not correlated with disease progression. These results suggest that TF was ubiquitously expressed in melanocytic cells and its expression was not correlated with disease progression and/or metastatic potency of melanoma cells. [source] Immunomagnetic detection of micrometastatic cells in bone marrow in uveal melanoma patientsACTA OPHTHALMOLOGICA, Issue 8 2009Nils Eide Abstract. Purpose:, Our objective was to introduce immunomagnetic separation (IMS) in ocular research by evaluating the possibility of detecting tumour cells in bone marrow (BM) and peripheral blood (PB) samples and validating the captured cells as melanocytic cells. Methods:, Mononuclear cell (MNC) fractions isolated from BM and PB in uveal melanoma patients were examined for tumour cells using our IMS method. Sheep-anti-mouse IgG antibody-coated super paramagnetic particles were conjugated to an anti-melanoma antibody. Microscopy of the magnetic fraction isolated from MNCs was performed to identify and count the number of bead-rosetted cells. The finding of at least two rosettes with coated beads in a 20-,l fraction of a sample was registered as a positive test. The melanocytic nature of the tumour cells was ascertained with a double labelling procedure using fluorescent microparticles. Results:, Using IMS in a study of 328 patients, tumour cells were at initial diagnosis found in BM and PB in 29.9% and 1.6% of cases, respectively. In positive samples, a median of 56 tumour cells (range 2,500) were identified. The captured cells were documented to be of melanocytic origin by the simultaneous binding of fluorescent beads coated with another melanoma-associated antibody. Conclusions:, The IMS method was sensitive and efficient in the detection of occult melanoma tumour cells in BM. The validity of the immunomagnetic technique was strengthened by verifying the melanocytic characteristics of the isolated cells. The IMS procedure identifies intact, vital tumour cells, permitting further molecular characterization, an advantage which makes this method attractive for extended use. The clinical relevance of the findings will be further investigated in follow-up studies with repeated sampling and characterization of the isolated tumour cells. [source] | |||||||||||||