Background: The pathophysiology of lichen sclerosus remains uncertain. The clinical features, including increased fragility and scarring, and the histology suggest that significant reorganisation of the extracellular matrix is occurring. Tenascin, fibrinogen and fibronectin are extracellular matrix components that play a significant role in tissue remodelling, for example during wound repair. Aim: To examine the distribution of tenascin, fibrinogen and fibronectin in vulval lichen sclerosus. Materials and Methods: Immunohistochemical staining was performed to study the distribution of tenascin, fibronectin and fibrinogen in 16 specimens of untreated vulval lichen sclerosus and 1 specimen of extragenital lichen sclerosus. Haematoxylin and eosin staining of the specimens was also performed to identify the position of the pale staining homogenous zone/zone of sclerosis and the inflammatory infiltrate below this. The control tissues studied included biopsies taken from the uninvolved thigh of 13 of the lichen sclerosus patients and 6 samples of normal vulva tissue obtained during gynaecological procedures from women of similar age to the lichen sclerosus women. Results: All the lichen sclerosus specimens demonstrated increased immunostaining of tenascin in the upper dermis and comparing this with the haematoxylin and eosin staining this corresponded to the zone of sclerosis with relatively little tenascin staining associated with the inflammatory band. In 14 out of the 16 vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen fibrinogen immunostaining was increased in the upper dermis which corresponded – in haematoxylin and eosin staining – to the zone of sclerosis. There was also slightly increased fibrinogen staining in the mid dermis which corresponded to the inflammatory band. Fibronectin staining was reduced in the upper dermis of 12 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen which corresponded to the zone of sclerosis. However, in 14 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen, fibronectin was slightly increased in the mid and deeper dermis which corresponded to the zone of inflammatory cells and the area below this. There was also increased fibronectin staining around blood vessel walls both in the mid dermis and within the zone of sclerosis. Conclusion: The distribution of tenascin, fibrinogen and fibronectin is altered in lichen sclerosus and the alteration in these extracellular matrix components may be relevant to the initiation of scarring in lichen sclerosus and the associated increased skin fragility.

1.
Marren P, Yell J, Charnock FM, Bunce M, Welsh K, Wojnarowska F: The association between lichen sclerosus and antigens of the HLA system. Br J Dermatol 1995;132:197–203.
2.
Walkden V, Chia Y, Wojnarowska F: The association of squamous cell carcinoma of the vulva and lichen sclerosus: Implications for management and follow-up. J Obstet Gynaecol 1997;17:551–553.
3.
Marren P, Dean D, Charnock M, Wojnarowska F: The basement membrane zone in lichen sclerosus: An immunohistochemical study. Br J Dermatol 1997;136:508–514.
4.
Mann PR, Cowan MA: Ultrastructural changes in four cases of lichen sclerosus et atrophicus. Br J Dermatol 1973;89:223–231.
5.
Kint A, Geerts ML: Lichen sclerosus et atrophicus. An electron microscopic study. J Cutan Pathol 1975;2:30–34.
6.
Carli P, Cattaneo A, Pimpinelli N, Cozza A, Bracco G, Giannotti B: Immunohistochemical evidence of skin immune system involvement in vulvar lichen sclerosus et atrophicus. Dermatologica 1991;182:18–22.
7.
Farrell AM, Marren P, Dean D, Jackson D, Wojnarowska F: Lichen sclerosus: Evidence that immunological changes occur at all levels of the skin. Br J Dermatol 1999;140:1087–1092.
8.
Carli P, Moretti S, Spallanzani A, Berti E, Cattaneo A: Fibrogenic cytokines in vulvar lichen sclerosus: An immunohistochemical study. J Reprod Med 1997;42:161–165.
9.
Gailit J, Clark R: Wound repair in the context of extracellular matrix. Curr Opin Cell Biol 1994;6:717–725.
10.
Chiquet-Ehrisman R, Mackie EJ, Pearson CA, Sakakura T: Tenascin: An extracellular matrix protein involved in tissue interaction during fetal development and oncogenesis. Cell 1986;47:131–139.
11.
Tuominen H, Pöllänen R, Kallioinen M: Multicentre origin of tenascin in skin tumors – An in situ hybridization study. J Cutan Pathol 1997;24:590–596.
12.
Schalkwijk J, Van Vlijmen I, Oosterling B, Perret C, Koopman R, van den Born J, Mackie J: Tenascin expression in hyperproliferative skin diseases. Br J Dermatol 1991;124:13–20.
13.
Farrell DH, Al-Mondhiry HA: Human fibroblast adhesion to fibrinogen. Biochemistry 1997;36:1123–1128.
14.
Soini Y, Pöllänen R, Autio-Harminen H, Lehto VP: Tenascin expression in lichen sclerosus. Int J Gynecol Pathol 1997;16:313–317.
15.
Lacour JP, Vitetta A, Chiquet-Ehrismann R, Pisani A, Ortonne JP: Increased expression of tenascin in the dermis in scleroderma. Br J Dermatol 1992;127:328–334.
16.
Tremaine R, Adam JE, Orizaga M: Morphea coexisting with lichen sclerosus et atrophicus. Int J Dermatol 1990;29:486–489.
17.
Lightner VA, Erickson HP: Binding of hexabrachion (tenascin) to the extracellular matrix and substratum and its effect on cell adhesion. J Cell Sci 1990;95:263–277.
18.
Chiquet-Ehrismann R, Kalla P, Pearson CA, Beck K, Chiquet M: Tenascin interferes with fibronectin action. Cell 1988;53:383–390.
19.
Makhluf HA, Stepniakowska J, Hoffman S, Smith E, LeRoy EC, Trojanowska M: IL-4 upregulates tenascin synthesis in scleroderma and healthy skin fibroblasts. J Invest Dermatol 1996;107:856–869.
20.
Sakai T, Kawakatsu H, Ohta M, Saito M: Tenascin induction in tenascin nonproducing carcinoma cell lines in vivo and by TGF-beta 1 in vitro. J Cell Physiol 1994;159:561–572.
21.
Rettig WJ, Erickson HP, Albino AP, Garin-Chesa P: Induction of human tenascin (neuronectin) by growth factors and cytokines: Cell type-specific signals and signalling pathways. J Cell Sci 1994;107:487–497.
22.
Farrell AM, Dean D, Wojnarowska F: Distribution of the transforming growth factor-β isoforms TGF-β1, TGF-β2 and TGF-β3 and vascular endothelial growth factor in vulval lichen sclerosus. J Reprod Med, in press.
23.
Gray AJ, Bishop JE, Reeves JT, Laurent GJ: Aα and Bβ chains of fibrinogen stimulate the proliferation of human fibroblasts. J Cell Sci 1993;104:409–413.
24.
Clark RAF: Fibronectin in the skin. J Invest Dermatol 1983;81:475–479.
25.
Morgan MB, Truitt CA, Taira J, Somach S, Pitha JV, Everett MA: Fibronectin and the extracellular matrix in the perforating disorders of the skin. Am J Dermatopathol 1998;20:147–154.
26.
Grinnell F, Billingham RE, Burgess L: Distribution of fibronectin during wound healing in vivo. J Invest Dermatol 1981;76:181–189.
27.
Frynad O: Studies on fibronectin in the skin. II. Indirect immuno fluorescence studies in psoriasis vulgaris. Arch Dermatol Res 1979;266:33–41.
28.
Wachtfogel YT, Abrams W, Kucich U, Weinbaum G, Shapira M, Colman RW: Fibronectin degradation products containing the cytoadhesive tetrapeptide stimulate human neutrophil degranulation. J Clin Invest 1981;81:1310–1316.
29.
Nathan C, Srimal S, Farber C, Sanchez E, Kabbash L, Asch A, Gailit J, Wright SD: Cytokine-induced respiratory burst of human neutrophils: Dependence on extracellular martrix proteins and CD11/CD18 integrins. J Cell Biol 1989;109:1341–1349.
30.
Clark RAF, Wikner NE, Doherty DE, Norris DE: Cryptic chemotactic activity of fibronectin for human monocytes resides in the 120-kDa fibroblastic cell-binding fragment. J Biol Chem 1988;263:12115–12123.
31.
Labat-Robert J, Birembaut P, Adnet JJ, Mercantini F, Robert L: Loss of fibronectin in human breast cancer. Cell Biol Int Rep 1980;4:608–616.
32.
Tremble P, Chiquet-Ehrismann R, Werb Z: The extracellular matrix ligands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts. Mol Biol Cell 1994;5:439–453.
33.
Frances C, Wechsler J, Meimon G, Labat-Robert J, Grimaud JA, Hewitt J: Investigation of intercellular matrix macromolecules involved in lichen sclerosus. Acta Derm Venereol (Stockh) 1983;63:483–490.
34.
Fleischmajer R, Dessau W, Timpl R, Krieg T, Luderschmidt C, Wiestner M: Immunofluorescence analysis of collagen, fibronectin and basement membrane protein in scleroderma skin. J Invest Dermatol 1980;75:270–274.
35.
Cooper SM, Keyser AJ, Beaulieu AD, Ruoslahti E, Nimni ME, Quismorio FP: Increase in fibronectin in the deep dermis of involved skin in progressive systemic sclerosis. Arthritis Rheum 1979;22:983–987.
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