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Coexpression of SOX10/CD271 (p75(NTR)) and β-Galactosidase in large to giant congenital melanocytic nevi of pediatric patients


Barysch, Marjam J; Levesque, Mitchell P; Cheng, Phil; Karpova, Maria B; Mihic-Probst, Daniela; Civenni, Gianluca; Shakhova, Olga; Sommer, Lukas; Biedermann, Thomas; Schiestl, Clemens; Dummer, Reinhard (2014). Coexpression of SOX10/CD271 (p75(NTR)) and β-Galactosidase in large to giant congenital melanocytic nevi of pediatric patients. Dermatopathology, 1(1):35-46.

Abstract

BACKGROUND: Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can transform into melanoma. However, this development is impeded in the majority of cases and mostly affects patients with large or giant CMNs.
METHODS: To elucidate mechanisms that keep CMNs from malignant transformation, CMN tissue biopsies were investigated for p-ERK and senescence markers by immunohistochemistry and for SOX10/CD271 (p75(NTR)) by immunofluorescence. CMN cells were cultivated, and MTT assays were performed for evaluating cell viability. Mutation status for NRAS and BRAF was performed by real-time PCR.
RESULTS: 13 CMNs (from patients aged 0.5-11.8 years, mean: 2.7) showed immunoreactivity for SOX10/CD271 (p75(NTR)) in 34.2%. p-ERK was immunoreactive in 80% (4/5); β-galactosidase was significantly stronger expressed in CMNs compared to melanocytic nevi of patients over 70 years (p = 0.0085). The 5 CMN cultures were immunoreactive for SOX10/CD271 (p75(NTR)) in 36.7%. By silencing SOX10 by siRNA in 2 CMN cell cultures, cell viability decreased significantly. NRAS(Q61K) mutation was found in 91.7% (11/12) and BRAF(V600E) in 6.3% of all analyzable CMNs (1/16).
CONCLUSIONS: Oncogene-induced senescence might prevent malignant transformation through activation of the mitogen-activated protein kinase pathway. SOX10 is necessary for the viability of human CMN cell cultures and may be responsible for clinical changes during aging.

Abstract

BACKGROUND: Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can transform into melanoma. However, this development is impeded in the majority of cases and mostly affects patients with large or giant CMNs.
METHODS: To elucidate mechanisms that keep CMNs from malignant transformation, CMN tissue biopsies were investigated for p-ERK and senescence markers by immunohistochemistry and for SOX10/CD271 (p75(NTR)) by immunofluorescence. CMN cells were cultivated, and MTT assays were performed for evaluating cell viability. Mutation status for NRAS and BRAF was performed by real-time PCR.
RESULTS: 13 CMNs (from patients aged 0.5-11.8 years, mean: 2.7) showed immunoreactivity for SOX10/CD271 (p75(NTR)) in 34.2%. p-ERK was immunoreactive in 80% (4/5); β-galactosidase was significantly stronger expressed in CMNs compared to melanocytic nevi of patients over 70 years (p = 0.0085). The 5 CMN cultures were immunoreactive for SOX10/CD271 (p75(NTR)) in 36.7%. By silencing SOX10 by siRNA in 2 CMN cell cultures, cell viability decreased significantly. NRAS(Q61K) mutation was found in 91.7% (11/12) and BRAF(V600E) in 6.3% of all analyzable CMNs (1/16).
CONCLUSIONS: Oncogene-induced senescence might prevent malignant transformation through activation of the mitogen-activated protein kinase pathway. SOX10 is necessary for the viability of human CMN cell cultures and may be responsible for clinical changes during aging.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:13 Jan 2017 12:58
Last Modified:14 Feb 2018 23:37
Publisher:Karger
ISSN:2296-3529
Additional Information:The final, published version of this article is available at http://www.karger.com/?doi=10.1159/000362490
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1159/000362490
PubMed ID:27047921

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