Immunohistochemical Labeling of Normal Melanocytes

Dean, Nicola R.; Brennan, J.G.; Haynes, Julie; Goddard, C.; Cooter, Rodney D.

doi:10.1097/00129039-200209000-00002

Cited by 20 publications

(17 citation statements)

References 24 publications

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“…Histologic maturation and regression of the PNs were observed in CMN subjected to serial skin biopsies over time. 13,15,37 In some of our cases, the proliferative nodules stained more intensely with melanocytic markers than the adjacent CMN. Several previous studies have also documented the relatively benign clinical course of PNs despite their worrisome clinical and pathologic appearance.…”

Section: Discussionmentioning

confidence: 50%

Proliferative Nodules in Congenital Melanocytic Nevi

Herron¹,

Vanderhooft²,

Smock³

et al. 2004

American Journal of Surgical Pathology

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Congenital melanocytic nevi (CMN) occur in 1% to 2% of newborns, and the risk of malignant melanoma is increased in patients with large CMN. Appearance at birth or later of a nodular or hyperpigmented area within a CMN simulates malignant melanoma and prompts biopsy. Although their clinical and pathologic features seem ominous, proliferative nodules (PNs) typically are benign and may regress, although atypical features cause greater concern. Here we report clinical and pathologic findings with outcome in 10 children who had multiple biopsies of large CMN with PNs. We reviewed 78 separate samples from the 10 patients and classified the 60 PNs according to published criteria. A subset of 30 samples containing both the CMN and a PNs was analyzed for immunohistochemical reactivity for melanocytic (S-100 protein, HMB45, melan-A), lymphocytic (CD45), cell-cycle/proliferative (Mib-1, p16, p21, p27, c-Myc), apoptotic (p53, Bax, c-kit, CD95), and anti-apoptotic (bcl-2) markers. Both CMN and PNs had similar expression of melanocytic, lymphocytic, and most cell-cycle/proliferative and apoptotic markers, including Mib-1, p16, p21, p27, c-Myc, Bax, CD95, and bcl-2. A greater proportion of PNs than CMN were reactive for p53 (67% vs. 30%, P < 0.0098) and c-kit (97% vs. 3%, P < 0.0001). p53 and p21 expression in CMN and all types of PNs were inversely correlated. When ordinary and atypical PNs were compared, the atypical PNs more frequently expressed p53, Mib-1, Bax, and bcl-2, but less frequently expressed p21. The c-kit expression in nearly all PNs and its absence in nearly all CMN is potentially useful for recognition of PN, suggests a delayed melanocytic maturation process in proliferative nodules, and may be likely indicative of their benign nature. p53 reactivity in concert with a lack of p21 up-regulation by immunohistochemistry suggests that a p53 mutation may be present in PN, although the immunohistochemical findings alone cannot exclude possible overexpression of wild-type p53. Regressive, involutional, or maturational changes were observed in sequential samples from 4 patients. No patient developed malignant melanoma or another melanocytic nevus-associated malignancy during the follow-up period. These findings underscore the similarities between PNs and the underlying CMN and suggest that maturational, proliferative, and apoptotic processes are involved in their clinical evolution.

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Section: Discussionmentioning

confidence: 50%

Proliferative Nodules in Congenital Melanocytic Nevi

Herron¹,

Vanderhooft²,

Smock³

et al. 2004

American Journal of Surgical Pathology

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“…Moreover, depending on the means of detection utilized, the number of melanocytes counted is deceptively low, because not all melanocytes actively produce melanin 28,29 . CISH showed that TRPM1 mRNA was expressed only by epidermal and follicular melanocytes.…”

Section: Resultsmentioning

confidence: 99%

“…26,27 Moreover, depending on the means of detection utilized, the number of melanocytes counted is deceptively low, because not all melanocytes actively produce melanin. 28,29 CISH showed that TRPM1 mRNA was expressed only by epidermal and follicular melanocytes. For normal melanocytes of the epidermis, TRPM1 mRNA was expressed in a relatively predictable pattern, averaging 1 TRPM1+ melanocyte to 10 basal keratinocytes (95% confidence interval or CI: 1 : 7 to 1 : 16).…”

Section: Expression Of Trpm1 and Melanin-related Proteins In Normal Skinmentioning

confidence: 99%

The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia‐associated transcription factor (MITF) and other melanogenesis‐related proteins in normal and pathological skin, hair follicles and melanocytic nevi

Slominski

Yang

et al. 2010

J Cutan Pathol

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Background Melastatin (TRPM1), a.k.a. transient receptor potential cation channel, subfamily M, member 1 (TRPM-1) regulates melanocyte differentiation and proliferation. TRPM1 is transcriptionally regulated by the essential melanocyte transcription factor MITF (microphthalmia-associated transcription factor). For the most part, MITF expression is preserved during melanoma progression, while TRPM1 mRNA expression decreases or is completely lost. The loss of TRPM1 is associated with melanomas that are more aggressive. Objective To assess the relationship between TRPM1 mRNA expression and the expression of MITF and nine other markers of melanocytes and melanin-related proteins by immunohistochemistry in normal skin, scars, hair follicles and ordinary melanocytic nevi. Methods Samples of normal skin (n = 102; from tumor excisions and plastic procedures), scars (n = 5; from re-excision specimens) and compound melanocytic nevi (n = 4) were evaluated for the presence of TRPM1 mRNA transcripts as detected by chromogenic in situ hybridization (CISH). Immunohistochemical techniques were used to detect melanin-related proteins including: MITF, S100 protein, Mart-1, tyrosinase, Mel5, HMB45, tyrosinase-related protein-1 (TRP1), TRP2 and α-melanocyte stimulating hormone (αMSH). The labeling index (LI) was defined as the number of intraepidermal cells expressing mRNA or protein per one hundred basal keratinocytes. Results A wide range of LI was found for all markers (0–33 positive cells/100 keratinocytes). When these LI were compared, no significant differences in the expression of MITF, S100, Mart1, tyrosinase proteins and TRPM1 mRNA were identified. The LI for TRPM1 mRNA expression ranged from 74% of that for MITF to 86% for tyrosinase. The LI for TRP-1, TRP-2 and Mel5 was similar to that of TRPM1, while HMB-45 had a significantly lower LI than all other markers. TRPM1 mRNA correlated most tightly with MITF and tyrosinase expression (r = 0.81 and 0.68, respectively, both p = 0.0001). Likewise, the strongest correlation among all the melanin-related proteins existed between tyrosinase and MITF (r = 0.79, p = 0.0001). There was variable expression of melanin-related proteins when LI were analyzed by anatomic site, patient age, extent of sun-damage and proximity to a melanocytic tumor. Anogenital skin showed the highest and acral skin the lowest LI for TRPM1, MITF, S100 protein, Tyrosinase, Mel5 and HMB45. Advanced age (>60 years) was associated with decreased TRPM1 expression. Sun-damaged skin exhibited significantly increased LI as measured by MITF, S100 protein, Mart1, tyrosinase and HMB-45, but no differences for TRPM1. However, the MITF-TRPM1 differential (i.e. MITF LI-TRPM1 LI = MITF+TRPM1 – melanocytes) was significantly increased in site-matched skin (4.6 ± 4.4 vs. 1.5 ± 2.5, p = 0.01). There was a suggestion of reduced LI in normal skin in the proximity of melanoma (from melanoma re-excision specimens) for S100, HMB45 and TRPM1 mRNA. TRPM1 LI was significantly decreased in scars compared to normal skin (5.6 ± 1....

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“…13 The polyclonal antibody to S-100 protein is routinely used to detect normal and altered melanocytes (melanomas), due to its high sensitivity. 17 However, in the skin, antibodies to S-100 protein are not specifi c for melanocytes, since they can also identify Langerhans and Schwann cells, 17,24 sensory corpuscles and sudoriparous gland cells. 24 In our skin model, the topography of S-100-positive cells among basal cells, together with the detection of pigment by Fontana-Masson silver impregnation is consistent with their melanocytic origin.…”

Section: Discussionmentioning

confidence: 99%

Immunoarchitectural characterization of a human skin model reconstructed in vitro

et al. 2009

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CONTEXT AND OBJECTIVE: Over the last few years, different models for human skin equivalent reconstructed in vitro (HSERIV) have been reported for clinical usage and applications in research for the pharmaceutical industry. Before release for routine use as human skin replacements, HSERIV models need to be tested regarding their similarity with in vivo skin, using morphological (architectural) and immunohistochemical (functional) analyses. A model for HSERIV has been developed in our hospital, and our aim here was to further characterize its immunoarchitectural features by comparing them with human skin, before it can be tested for clinical use, e.g. for severe burns or wounds, whenever ancillary methods are not indicated. DESIGN AND SETTING:Experimental laboratory study, in the Skin Cell

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Immunohistochemical Labeling of Normal Melanocytes

Cited by 20 publications

References 24 publications

Proliferative Nodules in Congenital Melanocytic Nevi

Proliferative Nodules in Congenital Melanocytic Nevi

The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia‐associated transcription factor (MITF) and other melanogenesis‐related proteins in normal and pathological skin, hair follicles and melanocytic nevi

Immunoarchitectural characterization of a human skin model reconstructed in vitro

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