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Coexpression of SOX10/CD271 (p75NTR) and beta-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 (p75NTR) and beta-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 > Institute of Anatomy
04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:14 Jul 2014 07:07
Last Modified:29 Aug 2017 14:28
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
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1159/000362490

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