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Published in: World Journal of Surgical Oncology 1/2018

Open Access 01-12-2018 | Research

Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma

Authors: Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H. Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari, Seppo Parkkila, Juha Saarnio, Petri P. Lehenkari, Tuomo J. Karttunen

Published in: World Journal of Surgical Oncology | Issue 1/2018

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Abstract

Background

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.

Methods

We investigated the expression and prognostic role of HIF-1alpha and CAIX in PDAC series from Northern Finland (n = 69) using immunohistochemistry.

Results

In 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.

Conclusions

Our 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.
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Metadata
Title
Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma
Authors
Joni Leppänen
Olli Helminen
Heikki Huhta
Joonas H. Kauppila
Joel Isohookana
Kirsi-Maria Haapasaari
Seppo Parkkila
Juha Saarnio
Petri P. Lehenkari
Tuomo J. Karttunen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2018
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-018-1432-4

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