Expression of hypoxia Inducible Factor 1α as a prognostic indicator in oesophageal cancer

  • Phanibhushana Munipalle

Student thesis: Doctoral Thesis

Abstract

Introduction Hypoxia Inducible Factor 1α (HIF 1α) plays a major role in the pleitropic response observed secondary to hypoxic conditions in tumours. Its expression in the tumour cells has been correlated to tumour aggressiveness but its prognostic value in squamous cell carcinoma (SCC) of the oesophagus remains unclear. To date, limited information is available on the prognostic role of HIF 1α in SCC of oesophagus in UK population. This information may help in choosing appropriate therapeutic strategies and possibly developing a monoclonal antibody with therapeutic potential targeting the HIF 1α. Methods Tumour samples from 36 patients diagnosed with SCC of oesophagus were collected in this prospective observational study. Prepared tissue sections were stained with validated specific monoclonal antibodies for HIF 1α in controlled experiment and the expression of HIF 1α was scored by blind assessment. This expression score was correlated with the disease pattern and survival over a period of 4 year 8 months. Results Out of 36 patients, 17 patients showed low and 19 high expression of HIF 1α. A trend of better median overall survival was observed in the group with low expression of HIF 1α compared to high expression (238 vs. 196 days) but this was not statistically significant (p>0.05, log rank test). Regression analysis showed that HIF 1α was not an independent prognostic factor for survival (p>0.05). Absence of metastases at diagnosis (p = 0.05) and treatment with curative intent (p = 0.001) were statistically significant prognostic factors on univariate analysis; on multivariate analysis, treatment with curative intent was the only independent statistically significant prognostic factor (p < 0.001). Conclusion HIF 1α expression did not show prognostic value in SCC of oesophagus in present study in spite of a trend in improved survival, in agreement with previous studies. Further study is required to support this observation. Similar knowledge on the role of HIF 1α expression in oeosphageal adenocarcinoma is scarce. As the incidence of adenocarcinoma is increasing, research in this field is recommended. Novel strategies on the therapeutic manipulation of HIF 1α in cancer are to be explored further and may have a role to play in improving treatment outcome in oesophageal cancer.
Date of Award16 Mar 2012
Original languageEnglish
Awarding Institution
  • Teesside University
SupervisorY. Viswanath (Supervisor), Marjorie Wilson (Supervisor), Julfiker Ali (Supervisor), Carolyn Summerbell (Supervisor) & Louisa Ells (Supervisor)

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