Expression of Hypoxia Inducible Factor-1α in Esophageal Squamous Cell Carcinoma and its correlation with clinicopathological parameters
Keywords:
esophageal carcinoma, immunohistochemistry, HIF-1α, chemoradiotherapy
Abstract
Background: Esophageal cancer is an aggressive tumour carrying a very poor prognosis. HIF-1α (Hypoxia induced factor) is an oxygen sensitive transcription factor which activates transcription of proangiogenic cytokines like VEGF (Vascular Endothelial Growth Factor) responsible for angiogenesis. In the present study we examined the HIF-1α expression in esophageal carcinoma cases and its correlation with various clinicopathological parameters. We also determined the clinical outcomes in such patients with chemoradiotherapy.Methods: The study was conducted on 50 cases of Esophageal Squamous Cell Carcinomas diagnosed in SGRDIMSAR, Amritsar. Detailed clinical data of the patient was recorded as per proforma attached. Tissue were formalin fixed, paraffin embedded and were studied for histopathological grading after staining with haematoxylin-eosin. All cases were subjected to immunohistochemistry for HIF-1α expression.Results: The maximum incidence was seen in age group of 41-60 years. Most of the cases were moderately differentiated 34 cases (68%) followed by poorly differentiated and well differentiated consisting of 20% and 12% respectively. The HIF-1α positivity was observed in 34 cases. 16/34 cases were classified as high score group. High HIF-1α expression significantly correlated with poor degree of differentiation(P=0.005), with the lymph node metastasis(P=0.015), lymhpatics invasion(P=0.018) and depth of invasion. Out of 20 patients resistant to therapy, 12 showed high HIF-1α score.Conclusion: The present study concluded that expression of HIF-1α was significantly correlated with poorer clinicopathological variables including higher grade, lymph node metastasis, lymphatics invasion and increased depth of tumour invasion. It was also determined that HIF-1α expression significantly correlates with an unfavourable prognosis in such patients treated with adjuvant chemoradiotherapy.References
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2. Rao DN, Sanghvi LD, Desai PB. Epidemiology of esophageal cancer. Semin Surg Oncol. 1989;5:351-4.
3. Ammigan, Nair UN, Lalitha VS, Bhinde SV. Carcinogenicity studies of masheri: pyrolysed tobacco product in vitamin A deficient Sprague-Dawley rats. J Cancer Res Clin Oncol. 1991;117:5-9.
4. Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem. 1994;269(38):23757–63.
5. Benizri E, Ginouves A, Berra E. The magic of the hypoxia-signaling cascade. Cell Mol Life Sci. 2008;65:1133-49.
6. Gordan JD, Simon MC. Hypoxia-inducible factors: central regulators of the tumor phenotype. Curr Opin Genet Dev. 2007;17:71-7.
7. Matsuyama T, Nakanishi K, Hayashi T, Yoshizumi Y, Aiko S, Sugiura Y, Tanimoto T, Uenoyama M, Ozeki Y, Maehara T. Expression of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma. Cancer Sci. 2005;96(3):176-82.
8. Kurokawa T, Miyamoto M, Kato K, Cho Y, Kawarada Y, Hida Y, Shinohara T, Itoh T, Okushiba T, Kondo S, Katoh H. Overexpression of hypoxia-inducible-factor 1a (HIF-1a) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Br J Cancer. 2003;89:1042–7.
9. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917.
10. Rohatagi P, Swisher SG, Cornea AM, Wu TT, Liao Z, Komaki R, Walsh GL, Vaporciyan AA, Rice DC, Roth JA, Ajani JA. Characterization of pathologic complete response after preoperative chemotherapy in carcinoma of the esophagus and outcome after pathologic complete response. Cancer. 2005;104:2365-72.
11. Eloubeidi MA, Desmond R, Arguedas MR, Reed CE, Wilcox CM. Prognostic factors for the survival of patients with oesophageal carcinoma in the U.S.: the importance of tumor length and lymph node status. Cancer. 2002;95:1434-43.
12. Youssef EM, Matsuda T, Takada N, Osugi H, Higashino M, Kinoshita H, Watanabe T, Katsura Y, Wanibuchi H, Fukushima S. Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer. 1995;76:358-66.
13. Parkin DM, Muir CS, Whelan SL, Gao YT, Ferlay J, Powell J. Cancer incidence in five continents. Lyon: International Agency for Research on Cancer; 1992.
14. Department of Health. National Cancer Registry Programme Annual report. New Delhi: Indian Council of Medical Research; 1990.
15. Cherian JV, Sivaraman R, Muthusamy AK, Jayanthi V. Carcinoma of the Esophagus in Tamil Nadu (South India): 16-year Trends from a Tertiary Center. J Gastrointestin Liver Di. 2007 Sep;16(3):245-9
16. Delima SL, McBride RK, Preshaw PM, Heasman PA, Kumar PS. Response of subgingival bacteria to smoking cessation. J Clin Microbiol. 2010;48(7):2344–9.
17. Wang DY, Xiang YY, Tanaka M, Li XR, Li JL, Shen Q, Sugimura H, Kino I. High prevalence of p53 protein overexpression in patients with esophageal cancer in Linxian, China and its relationship to progression and prognosis. Cancer. 1994;74:3089–96.
18. Takala H, Saarnio J, Wiik H, Ohtonen P, Soini Y. HIF-1α and VEGF are associated with disease progression in esophageal carcinoma. J Surg Res. 2011;167(1):41-8.
19. Koukourakis MI, Giatromanolaki A, Skarlatos J, Corti L, Blandamura S, Piazza M, Gatter KC, Harris AL. Hypoxia inducible factor (HIF-1α and HIF-2α) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy. Cancer Res. 2001;61:1830–2.
20. Ogawa K, Chiba I, Morioka T, Shimoji H, Tamaki W, Takamatsu R, Nishimaki T, Yoshmini N, Murayama S. Clinical Significance of HIF-1α Expression in Patients with Esophageal Cancer Treated with Concurrent Chemoradiotherapy. Anticancer Res. 2011;31:2351-60.
Published
2016-12-13
Section
Original Article
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