Aboushousha, T., Mamdouh, S., Hamdy, H., Helal, N., Khorshed, F., Safwat, G., Seleem, M. (2018). Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-Associated Hepatocellular Carcinomas. Asian Pacific Journal of Cancer Prevention, 19(1), 219-227. doi: 10.22034/APJCP.2018.19.1.219
Tarek Aboushousha; Samah Mamdouh; Hussam Hamdy; Noha Helal; Fatma Khorshed; Gehan Safwat; Mohamed Seleem. "Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-Associated Hepatocellular Carcinomas". Asian Pacific Journal of Cancer Prevention, 19, 1, 2018, 219-227. doi: 10.22034/APJCP.2018.19.1.219
Aboushousha, T., Mamdouh, S., Hamdy, H., Helal, N., Khorshed, F., Safwat, G., Seleem, M. (2018). 'Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-Associated Hepatocellular Carcinomas', Asian Pacific Journal of Cancer Prevention, 19(1), pp. 219-227. doi: 10.22034/APJCP.2018.19.1.219
Aboushousha, T., Mamdouh, S., Hamdy, H., Helal, N., Khorshed, F., Safwat, G., Seleem, M. Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-Associated Hepatocellular Carcinomas. Asian Pacific Journal of Cancer Prevention, 2018; 19(1): 219-227. doi: 10.22034/APJCP.2018.19.1.219
Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-Associated Hepatocellular Carcinomas
1Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt.
2Biochemistry Department, Theodor Bilharz Research Institute, Giza, Egypt.
3Surgical Department, Theodor Bilharz Research Institute, Giza, Egypt.
4Faculty of Biotechnology, October University of Modern Sciences and Arts, Giza, Egypt.
5National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
Receive Date: 09 October 2017,
Revise Date: 06 November 2017,
Accept Date: 15 December 2017
Abstract
Objective: To investigate the expression of TTF-1, RAGE, GLUT1 and SOX2 in HCV-associated HCCs and in surrounding non-tumorous liver tissue. Material and Methods: Tissue material from partial hepatectomy cases for HCC along with corresponding serum samples and 30 control serum samples from healthy volunteers were studied. Biopsies were classified into: non-tumor hepatic tissue (36 sections); HCC (33 sections) and liver cell dysplasia (LCD) (15 sections). All cases were positive for HCV. Immunohistochemistry (IHC), gene extraction and quantitative real-time reverse-transcription assays (qRT-PCR) were applied. Results: By IHC, LCD and HCC showed significantly high percentages of positive cases with all markers. SOX2 showed significant increase with higher HCC grades, while RAGE demonstrated an inverse relation and GLUT-1 and TTF-1 lacked any correlation. In nontumorous-HCV tissue, we found significantly high TTF-1, low RAGE and negative SOX2 expression. RAGE, GLUT-1 and SOX2 show non-significant elevation positivity in high grade HCV compared to low grade lesions. TTF-1, RAGE and SOX2 exhibited low expression in cirrhosis compared to fibrosis. Biochemical studies on serum and tissue extracts revealed significant down-regulation of RAGE, GLUT-1 and SOX2 genes, as well as significant up-regulation of the TTF-1 gene in HCC cases compared to controls. All studied genes show significant correlation with HCC grade. In non-tumor tissue, only TTF-1 gene expression had a significant correlation with the fibrosis score. Conclusion: Higher expression of TTF-1, RAGE, GLUT-1 and SOX2 in HCC and dysplasia compared to non-tumor tissues indicates up-regulation of these markers as early events during the development of HCV-associated HCC.
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