HIF-1a and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis
Published: May 1, 2016 | DOI: https://doi.org/10.7860/JCDR/2016/.7805
Dalia Rifaat Al-Sharaky, Asmaa Gaber Abdou, Moshira Mohammed Abdel Wahed, Hend Abdou Kassem
1. Lecturer, Department of Pathology, Faculty of Medicine, Menoufia University, Egypt.
2. Professor, Department of Pathology, Faculty of Medicine, Menoufia University, Egypt.
3. Professor, Department of Pathology, Faculty of Medicine, Menoufia University, Egypt.
4. Assistant Lecturer, Department of Pathology, Faculty of Medicine, Menoufia University, Egypt.
Correspondence
Dr. Dalia Rifaat Al-Sharaky,
Lecturer, Department of Pathology Faculty of Medicine, Menoufia University Shibeen El Koom,
32817 Menoufiya Governorate, Egypt.
E-mail: daliah_alsharaky@yahoo.com
Introduction: Hypoxia-Inducible Factor 1a (HIF-1a) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake.
Aim: To evaluate the immunohistochemical expression of both HIF-1a and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type.
Materials and Methods: A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1a and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks.
Statistical Analysis: Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS).
Results: HIF-1a was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1a expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1a H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1a staining in all cases of EC (p= 0.04).
Conclusion: The role of HIF-1a in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The stepwise increase in H- score of GLUT-1 in the studied cases implies its potential role in carcinogenesis of EC. HIF-1a may promote GLUT-1 expression in EC especially surrounding areas of necrosis. The differences between type I and type II EC regarding HIF-1a and GLUT-1 expression may confirm the differences in their aetiopathogenesis.
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