Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem cell phenotype
Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem cell phenotype
BACKGROUND: Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations, however the lineage of the mutated cells remains uncertain. This study was designed to test the hypothesis that CMN may be derived from cutaneous stem cells.
METHODS: Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (Nestin, Fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67), and MTOR/Wnt-signaling pathway activation (pS6, ?-catenin). Semi-quantitative scoring compared samples with naevus cell nesting (group 1) to those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples.
RESULTS: A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was significantly correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and stronger superficially. Expression of beta-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli.
CONCLUSIONS: CMN development frequently co-exists with normal overlying melanocyte development, leading us to hypothesise that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem cell origin, capable of some degree of melanocytic differentiation superficially.
374-383
Kinsler, V.A.
57360038-559b-4307-9df0-5e6a82ac6182
Anderson, G.
d810f0c8-17d8-4124-9eea-2a361d446aca
Latimer, B.
442f8398-472c-4c69-aa52-95ec4d3f3696
Natarajan, D.
79221191-30d2-4f2a-a326-c7d1c24a5bb8
Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd
Moore, G.E.
33dbde96-59e5-409d-b1ff-f3092991a3b9
Sebire, N.J.
66a7bcf0-1e60-4b0a-abdd-f5602f9b776b
August 2013
Kinsler, V.A.
57360038-559b-4307-9df0-5e6a82ac6182
Anderson, G.
d810f0c8-17d8-4124-9eea-2a361d446aca
Latimer, B.
442f8398-472c-4c69-aa52-95ec4d3f3696
Natarajan, D.
79221191-30d2-4f2a-a326-c7d1c24a5bb8
Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd
Moore, G.E.
33dbde96-59e5-409d-b1ff-f3092991a3b9
Sebire, N.J.
66a7bcf0-1e60-4b0a-abdd-f5602f9b776b
Kinsler, V.A., Anderson, G., Latimer, B., Natarajan, D., Healy, E., Moore, G.E. and Sebire, N.J.
(2013)
Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem cell phenotype.
British Journal of Dermatology, 169 (2), .
(doi:10.1111/bjd.12323).
(PMID:23517330)
Abstract
BACKGROUND: Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations, however the lineage of the mutated cells remains uncertain. This study was designed to test the hypothesis that CMN may be derived from cutaneous stem cells.
METHODS: Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (Nestin, Fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67), and MTOR/Wnt-signaling pathway activation (pS6, ?-catenin). Semi-quantitative scoring compared samples with naevus cell nesting (group 1) to those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples.
RESULTS: A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was significantly correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and stronger superficially. Expression of beta-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli.
CONCLUSIONS: CMN development frequently co-exists with normal overlying melanocyte development, leading us to hypothesise that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem cell origin, capable of some degree of melanocytic differentiation superficially.
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Accepted/In Press date: 12 March 2013
e-pub ahead of print date: 13 August 2013
Published date: August 2013
Organisations:
Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 351218
URI: http://eprints.soton.ac.uk/id/eprint/351218
ISSN: 0007-0963
PURE UUID: 92d9a7df-61ab-4a2a-a74a-c2978571746e
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Date deposited: 17 Apr 2013 10:01
Last modified: 14 Mar 2024 13:36
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Author:
V.A. Kinsler
Author:
G. Anderson
Author:
B. Latimer
Author:
D. Natarajan
Author:
G.E. Moore
Author:
N.J. Sebire
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