Immuno-histochemical evaluation of solar lentigines: The association of KGF/KGFR and other factors with lesion development

Received 6 April 2010; received in revised form 6 June 2010; accepted 14 June 2010. published online 12 July 2010.

Abstract

Background

Solar lentigines (SLs) are macular hyperpigmented lesions associated with sun exposure and age. Histopathologically, SLs are defined by a hyperpigmented basal layer and elongated rete ridges. The molecular mechanisms involved in the formation and the development of SLs are not completely understood. Our earlier data show that keratinocyte growth factor (KGF) induces hyperpigmentary lesions with histological resemblance to SLs.

Objective

To investigate the association of KGF/KGF receptor (KGFR) and other pigmentary genes with the progression of SL development. To better understand the possible role of KGF in the pathology of SLs.

Methods

Archived human skin biopsies (24 SLs and 14 healthy skins) were studied using immunohistochemistry for KGF/KGFR, proliferation marker Ki67, stem cell marker keratin-15 (K15), tyrosinase (TYR), stem cell factor (SCF), and protease-activated receptor-2 (PAR-2).

Results

An increase in TYR-positive cells and expression was found throughout SL progression, as compared to normal skin. The levels of KGF, KGFR, SCF, Ki67 and PAR-2 varied during SL progression. Ki67, K15 and KGF/KGFR were significantly upregulated at early-mid SL stages. The latest-stage SLs expressed the lowest levels of KGF, KGFR, SCF, Ki67 and PAR-2.

Conclusions

The upregulation of KGF/KGFR might induce the formation of rete ridges and hyperpigmentation. The reduced levels of all examined proteins (except TYR and K15) suggest a possible inactive status (dormancy or quiescence) of advanced lesions.

Abbreviations: SL, solar lentigines, F&M, Fontana Masson, IHC, immunohistochemistry, UV, ultraviolet, K15, keratin 15, KGF, keratinocyte growth factor, KGFR, KGF receptor, SCF, stem cell factor, TYR, tyrosinase, PAR-2, protease-activated receptor-2

Keywords: Solar lentigines, Hyperpigmentation, KGF, KGFR, Tyrosinase, K15

a The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, A Unit of Johnson & Johnson Consumer Companies, Inc., 199 Grandview Rd., Skillman, NJ 08558, USA

b Department of Pathology, Southern California Permanente Medical Group, Sunset Medical Center, Los Angeles, CA, USA

c Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

Corresponding author. Tel.: +1 908 874 2325; fax: +1 908 874 1254.

PII: S0923-1811(10)00198-2

doi:10.1016/j.jdermsci.2010.06.006

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