Nestin expression in cutaneous melanomas and melanocytic nevi

Brychtová, Světlana; Fiurásková, Michala; Hlobílková, Alice; Brychta, Tomáš; Hirnak, Jaroslav

doi:10.1111/j.1600-0560.2006.00627.x

Cited by 75 publications

(82 citation statements)

References 26 publications

(25 reference statements)

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“…It is downregulated upon terminal differentation of melanocytes, and appears to be a necessary cofactor for the expression of nestin, which has been correlated with tumor progression. [43][44][45] Given this, we hypothesized that SOX10 and/or nestin may have been differentially expressed in the two subtypes; the data did not support this theory.…”

Section: Discussionmentioning

confidence: 96%

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

et al. 2012

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Desmoplastic melanoma is subclassified into pure and mixed variants with a higher rate of lymph node metastasis in the latter. Given that reasons for these biological differences are not currently known, we investigated these subtypes with techniques that included genetic and immunohistochemical analyses of 43 cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13 and 17). Immunohistochemical stains were performed with antibodies to markers of significance with respect to biological potential of nevomelanocytic proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin, SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no mutations were found in any of the cases on analyses of exons 11, 13 and 17 of the c-KIT gene (P ¼ NS for all). For immunohistochemical analyses of pure versus mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d. ¼ 5.6) versus 28% (s.d. ¼ 12.6, Po0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases, Po0.01); nestin stained 83% (n ¼ 19/23 cases) versus 89% (16/18 cases, P ¼ NS); clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P ¼ NS); SOX10 87% (20/23 cases) versus 94% (17/18 cases, P ¼ NS) and CD271 stained 61% (14/23 cases) versus 67% (12/18 cases, P ¼ NS). Increased CD117 staining in the mixed variant suggests that alterations in the KIT protein may be involved in tumor progression. In addition, the proliferative index of the mixed variant was higher than that of the pure variant.

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Section: Discussionmentioning

confidence: 96%

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

et al. 2012

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“…16 Nestin, an intermediate filament protein expressed in the cytoplasm of neuroepithelial cells and a marker for neural progenitor cells in the central nervous system, has been described as a marker of melanocytic stem cells. [11][12][13][14] Previous studies have shown that there is an increased expression of this protein in malignant vs benign nevomelanocytic proliferations and that there appears to be a stepwise increase in the proportion of lesions expressing nestin from banal nevi to primary melanomas to metastatic melanoma. 12,13 More recently, nestin staining in stage I and II melanoma patients significantly predicted poor survival with lower rates in cases with nestin positivity in both tumoral and endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…3 Nestin, an intermediate filament protein expressed in the cytoplasm of neuroepithelial cells, is known to be a marker for neural progenitor cells in the central nervous system. [11][12][13][14] Recently described as a melanocytic stem cell marker, 12 nestin has been shown to have a significantly higher expression in melanomas compared with nevi and in metastatic melanomas compared with primary melanomas. [12][13][14] The primary aim of this study was to ascertain immunohistochemical expression of the ABC transporters ABCB5 and ABCF2 and, the stem cell marker, nestin in a spectrum of benign and malignant nevomelanocytic proliferations that ranged from banal nevi to invasive primary cutaneous melanomas to assess whether they played a role in the development of malignancy.…”

mentioning

confidence: 99%

Profiling of ABC transporters ABCB5, ABCF2 and nestin-positive stem cells in nevi, in situ and invasive melanoma

et al. 2012

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Distinct ABCB5 forms and ABCF2, members of the ATP-binding cassette (ABC) superfamily of transporters, are normally expressed in various tissues and cells, and enhanced expression of both has been demonstrated in select cancers. In melanoma cell lines, gene expression profiling of ABC transporters has revealed enhanced expression of melanocyte-specific ABCB5 and ABCF2 proteins. Given this, our primary aim was to ascertain immunohistochemical expression of the ABC transporters ABCB5 and ABCF2 and, the stem cell marker, nestin in a spectrum of benign and malignant nevomelanocytic proliferations, including nevi (n ¼ 30), in situ (n ¼ 31) and invasive (n ¼ 24) primary cutaneous melanomas to assess their role in the stepwise development of malignancy. In addition, their expression was compared with established melanoma prognosticators to ascertain their utility as independent prognosticators. A semiquantitative scoring system was utilized by deriving a cumulative score (based on percentage positivity cells and intensity of expression) and statistical analyses was carried out using analysis of variance with linear contrasts. Mean cumulative score in nevi, in situ and invasive melanoma were as follows: 3.8, 4.4 and 5.3 for ABCB5, respectively (Po0.005 for all), and 4.6, 4.6 and 5.3 for nestin, respectively (P ¼ not significant for all). No appreciable expression of ABCF2 was noted in any of the groups. While ulcerated lesions of melanoma demonstrated lower levels of expression of ABCB5 and nestin than non-ulcerated lesions, and nestin expression was lower in lesions with mitoses 41, after controlling for the presence of ulceration and mitotic activity, the expression of both proteins did not significantly correlate with known melanoma prognosticators. The gradual increase in the expression of ABCB5 from benign nevus to in situ to invasive melanoma suggests that it plays a role in melanomagenesis. On the basis of our findings, a prospective study with follow-up data is required to ascertain the utility of ABCB5 as a therapeutic target.

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“…136 Nestin expression is associated with cell migration and metastasis in prostate cancer, 137 and tumor progression and deceased survival in melanoma. 41,[138][139][140][141][142] Nestin and SOX2, 143 an embryologic stem cell transcription factor that binds an enhancer region on the nestin gene, 144 are preferentially coexpressed in metastatic melanomas when compared with nevi or primary melanomas. 145 Moreover, SOX2-positive melanoma cells tend to be more spindleshaped cells and to have a more peripheral nestin pattern, which may represent a motile, more mesenchymal phenotype.…”

Section: How Primitive Melanoma Cells May Encourage 'Vasculogenic Mimmentioning

confidence: 99%

Melanoma stem cells: not rare, but well done

Girouard

Murphy

2011

Laboratory Investigation

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Since the identification of self-renewing cells in the hematopoietic system, stem cells have transformed the study of medicine. Cancer biologists have identified stem-like cells in multiple malignancies, including those of solid organs. This has led to the development of a stem cell theory of cancer, which purports that a subpopulation of self-renewing tumor cells is responsible for tumorigenesis. This contrasts with the stochastic model of tumor development, which advances that all tumor cells are capable of tumor formation. Within the field of melanoma, the identity and existence of cancer stem cells has been the subject of recent debate. Much of the controversy may be traced to differences in interpretations and definitions related to the cancer stem cell theory, and the use of dissimilar methodologies to study melanoma cells. Accumulating evidence suggests that cancer stem cells may exist in melanoma, although their frequency may vary and they may be capable of phenotypic plasticity. Importantly, these primitive melanoma cells are not only capable of self-renewal and differentiation plasticity, but also may confer virulence via immune evasion and multidrug resistance, and potentially via vasculogenic mimicry and transition to migratory and metastasizing derivatives. Therapeutic targeting of melanoma stem cells and the pathways that endow them with virulence hold promise for the design of more effective strategies for amelioration and eradication of this most lethal form of skin cancer.

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Nestin expression in cutaneous melanomas and melanocytic nevi

Abstract: We conclude that expression of the intermediate filament protein nestin might be an indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore, we suggest that nestin might be a relevant marker of tumorous and non-tumorous angiogenesis.

Cited by 75 publications

References 26 publications

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal

Profiling of ABC transporters ABCB5, ABCF2 and nestin-positive stem cells in nevi, in situ and invasive melanoma

Melanoma stem cells: not rare, but well done

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