Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma

Bakos, Renato Marchiori; Maier, Tanja; Besch, Robert; Mestel, Dominik; Ruzicka, Thomas; Sturm, Richard A.; Berking, Carola

doi:10.1111/j.1600-0625.2009.00991.x

Cited by 62 publications

(71 citation statements)

References 31 publications

(41 reference statements)

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“…Besides morphological and histopathological markers, several molecular markers have diagnostic and prognostic utility (1). These include markers on the melanoma, for example methylthioadenosine phosphorylase (MTAP) (2), nestin and SOX9 (3), and markers in patients' blood, for example p-proteasome levels (4). The search for a prognostic marker continues, however.…”

Section: Introductionmentioning

confidence: 99%

Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma

Hassel

Amann

Schadendorf

et al. 2013

Experimental Dermatology

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Metabolism inside cells differs between cancer and normal cells. Because disturbance of vitamin A metabolism might be important, we investigated expression of the enzymes lecithin retinol acyltransferase (LRAT) and RPE65 by immunohistochemistry in melanoma metastases and melanocytic nevi. Semiquantitative evaluation of this expression revealed downregulated expression of RPE65 in malignant melanoma compared with benign melanocytic nevi (P < 0.001). In contrast, expression of LRAT was not significantly different (P = 0.339).High LRAT expression in melanoma metastases was inversely correlated with patient survival; Kaplan-Meier analysis revealed earlier melanoma-related death (P = 0.003). Expression of LRAT might, therefore, be a prognostic marker of the clinical course of melanoma.

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Section: Introductionmentioning

confidence: 99%

Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma

Hassel

Amann

Schadendorf

et al. 2013

Experimental Dermatology

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“…A few studies have demonstrated that the neural stem/progenitor cell marker nestin, a type VI intermediate filament transiently expressed in early migrating and proliferating neuroectodermal cells, 18 is expressed in primary and metastatic melanomas. [19][20][21][22][23] Furthermore, this expression seem to correlate with more advanced disease and decreased 5-year survival. 24,25 In contrast, the majority of melanocytic nevi, even dysplastic nevi, showed no or weak nestin staining.…”

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confidence: 99%

Diagnostic utility of neural stem and progenitor cell markers nestin and SOX2 in distinguishing nodal melanocytic nevi from metastatic melanomas

Chen

et al. 2013

Modern Pathology

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Sentinel lymph node evaluation is a critical component of melanoma staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. One of the well-known diagnostic pitfalls in melanoma sentinel lymph node evaluation is the presence of nodal melanocytic nevi, which has been demonstrated in up to 26% of lymphadenectomy specimens and specifically in melanoma patients. Melanocytic markers enhance the sensitivity of melanoma detection in sentinel lymph nodes. However, established markers such as anti-melan-A/MART1, S100 protein and SOX10 antibodies cannot discriminate melanoma metastasis from nodal nevi. Recent studies have demonstrated strong expression of neural stem/progenitor cell markers nestin and SOX2 in melanoma. In this study, we tested the diagnostic utility of nestin and SOX2 in differentiating metastatic melanomas from nodal nevi. Twenty-three lymph nodes with metastatic melanomas and 17 with nodal nevi were examined. Of the 23 metastatic melanomas, 18 showed diffuse and strong (3 þ ) nestin, 4 showed rare cells with strong (3 þ ) nestin, and one showed diffuse but faint (1 þ ) nestin staining. Nuclear SOX2 was positive in 13 metastatic melanomas. In contrast, 15 nodal nevi showed no nestin, and 2 showed rare cells with very faint (o1 þ ) nestin staining. SOX2 was negative in 13 nodal nevi. Overall, nestin was strongly expressed in metastatic melanomas (n ¼ 22/23; 96%), but not in nodal melanocytic nevi (n ¼ 15/17; 88%; Po0.0001). SOX2 was also expressed in metastatic melanomas (n ¼ 13/23; 57%) but not in the majority of nodal melanocytic nevi (n ¼ 13/16; 81%; P ¼ 0.02). In one lymph node harboring metastatic melan-A-negative desmoplastic melanoma, nestin and SOX2 strongly highlighted the infiltrating tumor cells, suggesting the potential clinical value of these two markers in desmoplastic melanoma lymph node biopsies. This study provides evidence that nestin and SOX2 can effectively differentiate nodal melanocytic nevi from metastatic melanomas and serve as powerful diagnostic adjuncts in melanoma staging. Modern Pathology (2013) 26, 44-53; doi:10.1038/modpathol.2012; published online 17 August 2012Keywords: metastatic melanomas; nestin; nodal melanocytic nevi; SOX2 Malignant melanoma is a malignant tumor of melanocytes that accounts for less than 10% of all skin cancer diagnoses but the majority of skin cancerrelated deaths. 1 For patients diagnosed with malignant melanoma, sentinel lymph node biopsy is an essential component of tumor staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. [2][3][4] When melanoma metastasizes, a regional lymph node is the most common site, and tumor burden can range from rare tumor cells to complete effacement of lymph nodes. The presence of either micro-or macrometastasis in a single lymph node changes melanoma staging from stage I to stage III. 5 In addition, a single positive lymph node signifies a decrease in 10-year survival from 95% (stage IA) to 68% (stage II...

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“…Nestin was also co-expressed with SOX9 and SOX10, which may contribute to its transcriptional up-regulation, in primary and secondary melanoma specimens and associated with a poor survival of melanoma patients [98][99][100][101] . The analyses by flow cytometry and quantitative reverse transcription-PCR (qRT-PCR) of the expression level of nestin performed on 23 tissue specimens from patients with stage Ⅲ-Ⅳ melanoma has also indicated that this stem cell-like marker was expressed at a higher level in stage Ⅳ patients compared to stage Ⅲ /Ⅳ with no evidence of disease [93] .…”

Section: Potential Biomarkers In Melanoma Stem/progenitor Cellsmentioning

confidence: 99%

“…The immunohistochemical analysis of nestin, which is a neuroepithelial intermediate filament expressed in proliferative neuroectodermal progenitor cells during embryonic development and adult bulge areas-resident stem cells in hair follicle, has also indicated that its expression was significantly enhanced in primary and metastatic melanoma tissue specimens as compared to benign and normal melanocytes [96][97][98][99][100][101] . Nestin was also co-expressed with SOX9 and SOX10, which may contribute to its transcriptional up-regulation, in primary and secondary melanoma specimens and associated with a poor survival of melanoma patients [98][99][100][101] .…”

Section: Potential Biomarkers In Melanoma Stem/progenitor Cellsmentioning

confidence: 99%

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

Mimeault

Batra²

2012

WJCO

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Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cellbased therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transformation of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-RafV600E and N-RasQ61R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor (EGFR), stem cell-like factor (SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF)/ VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition (EMT)-associated molecules, including phosphatidylinositol 3'-kinase (PI3K)/Akt/ molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), macrophage inhibitory cytokine-1 (MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.

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Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma

Cited by 62 publications

References 31 publications

Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma

Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma

Diagnostic utility of neural stem and progenitor cell markers nestin and SOX2 in distinguishing nodal melanocytic nevi from metastatic melanomas

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

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