Quantitative comparison of angiogenesis and lymphangiogenesis in cutaneous lichen planus and psoriasis: Immunohistochemical assessment

Abstract

Recent experimental studies revealed that angiogenesis and lymphangiogenesis are closely related to chronic inflammation. The present study aims to evaluate quantitative changes of blood and lymphatic microcirculatory beds in cutaneous lichen planus (CLP) and psoriatic lesions using immunohistochemical analysis with antibodies to CD34, D2-40 and VEGF. Morphometric software was used to determine the area of blood and lymphatic vessels (BVA and LVA) and also the VEGF positive area. Statistical analysis of these parameters confirmed a significant enlargement of both the blood and lymphatic microcirculatory beds in psoriatic and CLP lesions. BVA in CLP lesions was increased by 56% however this augmentation was not as great as in psoriatic lesions where BVA was increased by 123%. Interestingly, LVA in psoriatic and CLP lesions was increased equally by 85%. The strongest VEGF expression was detected in psoriatic lesions, with lower, but still significant, overexpression in CLP lesions. VEGF-C was significantly increased in both psoriatic and CLP lesions in comparable level. Noticeably higher VEGF and VEGF-C expression was observed in the epidermis than in the dermis. Finally, our results indicate that the level of angiogenesis is considerably greater in psoriatic lesions than in CLP lesions, but the level of lymphangiogenesis is equal in both psoriatic and CLP lesions.

Introduction

The cutaneous microcirculation in healthy adults is predominantly quiescent, due to the dominant influence of endogenous angiogenesis inhibitors over the stimuli. However it retains the capacity for brisk initiation of angiogenesis and lymphangiogenesis in specific physiological and pathological conditions.

Experimental studies have revealed that angiogenesis and lymphangiogenesis are tightly connected, not only in tumor biology, but also in chronic inflammation. Pathological angiogenesis or lymphangiogenesis was confirmed in skin tumors: melanoma (Hannah and Folkman, 1996, Marcoval et al., 1996, Kashani-Sabet et al., 2002, Jonjic et al., 2003), basal cell carcinoma (Staibano et al., 1996), Kaposi's sarcoma (Kang et al., 2008), hemangioma (Boye et al., 2001) as well as in chronic dermatoses such as rosacea (Aroni et al., 2008), atopic dermatitis (Zhang et al., 2006, Genovese et al., 2012) and especially in psoriasis (Braverman and Sibley, 1982, Creamer et al., 1997, Creamer et al., 2002a, Heidenreich et al., 2009).

Both psoriasis and cutaneous lichen ruber planus (CLP) are relatively common chronic inflammatory dermatoses with unclear etiology and not entirely understood pathogenesis. Both of these dermatoses are classified in the group of primarily T-lymphocyte – driven diseases (Braun-Falco et al., 2001). Both psoriasis and cutaneous lichen planus show key histopathological changes in lesional epidermis and concomitant inflammatory changes within the dermis.

Histopathological manifestation of CLP includes epidermal hyperkeratosis with zonal wedge-shaped hypergranulosis and little or no parakeratosis, the basal cells vacuolar alteration, acanthosis and colloid bodies as anucleated remnants of apoptotic basal keratinocytes. A band like lymphocytic infiltrate occupies the widened papillary dermis and may be admixed with melanophages (Murphy, 1995, Lehman et al., 2009, Joshi, 2013).

Major characteristics of lesional psoriatic skin include epidermal hyperplasia with elongated rete ridges, abnormal differentiation of the keratinocytes, spongiosis, parakeratosis and hypogranulosis. Within the dermis there is an accumulation of inflammatory cells, especially T-lymphocytes, monocytes and neutrophils, and prominent expansion of the superficial vascular plexus with high and tortuous capillary loops within the dermal papillae (Braverman and Sibley, 1982, Braun-Falco et al., 2001, Murphy et al., 2007).

Currently there is increasing evidence that psoriasis is an angiogenesis – dependent disease, however microvascular changes in cutaneous lichen planus are rarely reviewed. Angioproliferation was confirmed only in mucous-oral lichen planus (Scardina et al., 2007a, Scardina et al., 2007b, Scardina et al., 2011, Tao et al., 2007, Scardina and Mesina, 2009). Therefore the objective of the present study was the immunohistochemical assessment of quantitative changes of both the blood and lymphatic microcirculatory beds within CLP lesions and its comparison with psoriatic lesions and healthy skin.