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Abstract BCC and SCC are the common malignant neoplasms of the skin. BCC is characterized by local invasion and contiguous spread. SCC is a biologically aggressive tumor and usually metastasizes. Following local invasion and tissue destruction, SCC commonly metastasizes to lymph nodes. Lysyl oxidase gene family comprises five members acting as extracellular modulating enzymes: LOX, LOXL, LOXL2, LOXL3, and LOXL4. It is a copper-dependent amine oxidase that initiates the covalent cross-linking of collagens and elastin in extracellular matrices (ECM). LOX is secreted as a glycosylated proenzyme, processed by procollagen C-proteinase into a mature active form. LOX activity modulation, due to either an increase or a decrease in its expression, induces multiple effects on the structure and major characteristics of the ECM. LOX is essential in maintaining the characteristics of blood vessels and arteries, where its activity modulation is correlated to atherosclerosis aneurism and human arterial dissection. LOX down-regulation is correlated to many connective tissue disorders seen in Ehler-Danlos syndrome, cutis laxa, and Menke’s syndrome. In tumors, LOX up-regulation is found in the stromal reaction observed around tumor foci in ductal breast carcinomas and in bronchopulmonary carcinomas. Lysyl oxidase like 2 (LOXL2), similar to its other LOX family members, has been reported to have amine oxidase activity, but unlike its family members, its enzyme activity was not inhibited by beta-aminoproprionitrile (BAPN). Its overexpression in a number of cancer and its ability to promote epithelial to mesenchymal transition suggest that LOXL2 might play a role in tumor progression. The aim of the present study was to investigate the role of LOXL2 in the pathogenesis of hyperproliferative skin diseases including NMSC and psoriasis through its immunohistochemical localization in skin biopsies of these disease entities. This prospective and retrospective case - control study included 70 patients. These included 20 cases with BCC and 20 cases with SCC. Control group included 10 healthy subjects and 20 subjects with psoriasis. Cases of BCC, SCC, and psoriasis were selected from Dermatology Outpatient Clinic, Menoufia University Hospital during the period from June 2014 to May 2016. For the retrospective part of the study, tissue blocks of archived cases in Pathology Department were used. Normal skin samples were obtained from subjects attending Plastic Surgery Department. A written consent form approved by the Local Ethical Research Committee in Menoufia Faculty of Medicine was obtained from every subject before the study initiation. All patients were subjected to detailed history taking and dermatological examination. Biopsies were taken from all cases and control subjects. Routine histopathological examination with H&E stain was done as well as immunohistochemical staining to evaluate the expression of LOXL2 antigen by using Rabbit polyclonal antibody. All control subjects (normal skin biopsies and patients with psoriasis as an example of benign hyper proliferative skin diseases) showed positive LOXL2 immunoreactivity.(100%) in normal skin and (75%) in psoriatic cases. LOXL2 was expressed in overlying epidermis in 85 % and80% of BCC and SCC cases respectively.It was expressed in tumour islands in 95% and 100% of BCC and SCC respectively. All positive cases of BCC had cytoplasmic pattern and patchy distribution in overlying epidermis and tumour islands respectively. 2 cases of BCC (11.8%) had cytoplasmic pattern with perinuclear condensation in overlying epidermis . Intensity was mild in all positive cases of BCC in overlying epidermis. Intensity of expression varied from mild-moderate in 17 cases of BCC (89.5%), mild strong in 1 case (5.3 %) and moderate strong in 1 case (5.3%) in tumour islands . Positive dermal immunoreactivity was noted in all cases of BCC. Five cases of SCC (31.3%) had cytoplasmic pattern and 9 cases (56.3%) had membrano-cytoplasmic pattern, and 1 case (6.3%) had membranonuclear pattern and 1 case (6.3%) had nuclear pattern in overlying epidermis. 17 cases of SCC (85%) had cytoplasmic pattern and 3 cases (15%) had membranocytoplasmic pattern in tumour islands. Positive dermal immunoreactivity was noted in all cases of SCC. |