Evaluation of Hypoxia Inducible Factor-1α and Glucose Transporter-1 Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study

Introduction: Hypoxia Inducible Factor-1 (HIF-1) is a mediator enabling cell adaptation to hypoxia. It plays its role mainly through transcription of many target genes including Glucose Transporter-1 (GLUT-1) gene. Aim: The present work aimed at evaluating the pattern and distribution of HIF-1 alpha and GLUT-1 in each case and control. Materials and Methods: A case-control and retrospective study was conducted on archival blocks diagnosed from pathology department as, Basal Cell Carcinoma (BCC, 20 cases), cutaneous Squamous Cell Carcinoma (SCC, 20 cases) and 20 normal site-matched skin biopsies from age and gendermatched healthy subjects as a control. Evaluation of both HIF-1 alpha and GLUT1 expression using standard immunohistochemical techniques was performed on cut sections from selected paraffin embedded blocks. Results: HIF-1 alpha was expressed in 90%, 35% 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 alpha and GLUT-1 localization in tumour nests was central, peripheral or central and peripheral. Both HIF-1 alpha 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 alpha and those of GLUT-1 in tumour islands or in overlying epidermis either in BCC or SCC. Conclusion: HIF-1 alpha may have a role in NMSC pathogenesis through adaptation to hypoxia which results from excessive proliferation. GLUT-1 down regulation in NMSC may be explained by its consumption by proliferating tumour cells. The expression of HIF-1 alpha and GLUT-1 in normal epidermis, stromal and adnexal structures needs further research.