Introduction Hypoxia Inducible Factor-1 (HIF-1) is a mediator enabling cell adaptation to hypoxia. and 100% of normal skin, BCC and SCC tumour islands respectively. It was up regulated in both BCC and SCC compared with normal skin (p= 0.001, p 0.001 respectively). GLUT-1 was expressed in 100%, 70% and 100% of normal skin, BCC and SCC tumour islands respectively. It was down regulated in Non Melanoma Skin Cancer (NMSC) cases compared with normal skin (p=0.004). HIF-1 and GLUT-1 NVP-BGJ398 enzyme inhibitor localization in tumour nests was central, peripheral or central NVP-BGJ398 enzyme inhibitor and peripheral. Both HIF-1 and GLUT-1 showed variable expression in stroma, adnexa and inflammatory cells. No significant correlation was found between Histo (H) score or expression percentage values of HIF-1 and those of GLUT-1 in tumour islands or in overlying epidermis either in BCC or SCC. Conclusion HIF-1 may have a role in NMSC pathogenesis through adaptation to hypoxia which results NVP-BGJ398 enzyme inhibitor from excessive proliferation. GLUT-1 down regulation in NMSC may be explained by its consumption by proliferating tumour cells. The expression of HIF-1 and GLUT-1 in normal epidermis, stromal and adnexal structures needs further research. strong class=”kwd-title” Keywords: Basal cell carcinoma, Pathogenesis, Squamous cell carcinoma Introduction NMSC, consisting of BCC and SCC, is 18-20 occasions more frequent than cutaneous malignant melanoma [1]. According to The Egyptian Pathology-Based Malignancy Registry (2001-2010), NMSC in Egypt represented 4.4% of total malignancies [2]. Hypoxia plays a vital role in carcinogenesis. In tumour microenvironment, metabolic reprogramming and changes in gene expression are necessary for adaptation to decreased oxygen availability. HIFs being oxygen sensitive transcription factors help in adaptation to hypoxic environment. They are important mediators of cellular response to stress. Metabolic changes occurring during tumourigenesis are, in part, under hypoxia and HIFs regulation. Moreover, inflammatory signaling and infiltration secondary to hypoxia are clear drivers of tumour progression [3]. HIF-1 is the intrinsic survival factor of tumour cells to overcome oxygen and nutrient deficits during proliferation and progression [4] through mediation of the transcription of over 200 target genes, including genes of Vascular Endothelial Growth Factor (VEGF) and GLUT-1 [5]. It induces expression of target genes by DNA binding in the area of Hypoxia Response Element (HRE) which gives rise to a series of subsequent processes like inhibition of apoptosis, switch to anaerobic metabolism, angiogenesis, cell proliferation and erythropoiesis, all of which activate carcinogenesis and metastasis [6]. HIF-1 is usually a heterodimeric protein consisting of a constitutively expressed -subunit (HIF-1) and -subunit (HIF-1). Under hypoxia, HIF-1 is usually stabilized and dimerizes with HIF-1 interacting with the co-activator CBP/p300 to bind to the HRE around the promoter regions in various target genes [7,8]. GLUT-1 is the most common glucose transporter in humans. It facilitates the transport of glucose across NVP-BGJ398 enzyme inhibitor the plasma membranes of mammalian cells [9] and is responsible for the low level of basal glucose uptake required to sustain respiration in all cells [10]. Previous studies indicated that upregulation of GLUT-1 contributed to improve glucose metabolism in rapidly proliferating malignancy cells [9], which are energy-dependent [11]. This study aimed at evaluating the pattern and distribution of HIF-1 and GLUT-1 expression in NMSC and their relationship with clinicopathologic parameters of selected cases. Materials and Methods This case-control study included 60 subjects (20 cases with nodular BCC, 20 cases with cutaneous SCC and 20 age and sex-matched healthy subjects as a control group). Cases of BCC and SCC were selected from Dermatology Outpatient Medical center, Menoufiya University Hospital, Egypt during the period from March 2014 to March 2015. For the retrospective part of the study, tissue blocks of archived cases in Pathology Department, Menoufiya University were used. Normal skin NVP-BGJ398 enzyme inhibitor samples were obtained from subjects attending Plastic Surgery Department. Biopsies from cases and control subjects were site-matched. Clinical data Rabbit Polyclonal to MAP3K7 (phospho-Thr187) describing patients demographics (age and gender) as well as the clinical variables (site, size of lesions and disease duration) were obtained and documented. Ethics 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. This was also in accordance with the Helsinki Declaration of 1975 (revised in 2000). Histopathological Examination of H&E Stained.