Abstract
BackgroundHIF-1alpha and CAIX proteins are commonly expressed under hypoxic conditions, but other regulatory factors have been described as well. Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxia and strong stromal reaction and has a dismal prognosis with the currently available treatment modalities.MethodsWe investigated the expression and prognostic role of HIF-1alpha and CAIX in PDAC series from Northern Finland (n = 69) using immunohistochemistry.ResultsIn our PDAC cases, 95 and 85% showed HIF-1alpha and CAIX expression, respectively. Low HIF-1alpha expression correlated with poor prognosis, and multivariate analysis identified weak HIF-1alpha intensity as an independent prognostic factor for PDAC-specific deaths (HR 2.176, 95% CI 1.216–3.893; p = 0.009). There was no correlation between HIF-1alpha and CAIX expression levels, and the latter did not relate with survival.ConclusionsOur findings are in contrast with previous research by finding an association between low HIF-1alpha and poor prognosis. The biological mechanisms remain speculative, but such an unexpected relation with prognosis and absence of correlation between HIF-1alpha and CAIX suggests that the prognostic association of HIF-1alpha may not directly be linked with hypoxia. Accordingly, the role of HIF-1alpha might be more complex than previously thought and the use of this marker as a hypoxia-related prognostic factor should be addressed with caution.
Highlights
HIF-1alpha and Carbonic anhydrase (CAIX) proteins are commonly expressed under hypoxic conditions, but other regulatory factors have been described as well
HIF-1alpha and CAIX are expressed in normal pancreas and in pancreatic ductal adenocarcinoma For HIF-1alpha staining, normal pancreatic tissue adjacent to Pancreatic ductal adenocarcinoma (PDAC) was present in 35/64 cases
Positive nuclear HIF-1alpha staining was more prevalent and extensive in cancerous tissue, where it was found in 61/64 (95%) cases, as compared with the adjacent normal pancreatic tissue; (p < 0.001) (Fig. 1a, c, d)
Summary
HIF-1alpha and CAIX proteins are commonly expressed under hypoxic conditions, but other regulatory factors have been described as well. Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxia and strong stromal reaction and has a dismal prognosis with the currently available treatment modalities. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide [1]. Surgical and oncological treatment of PDAC is arduous for the patient but still, the long-term survival rates are low [2]. Surgical resection [3], often in combination with adjuvant chemotherapy [4], is the only curative treatment of PDAC. PDAC is characterized by hypoxia and neovascularization [5, 6]. Hypoxia-inducible factor 1 alpha (HIF-1alpha) is a protein expressed under hypoxic conditions [7]. HIF-1alpha regulates tumor angiogenesis [8], and high
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call