University of Oulu

Leppänen, J., Helminen, O., Huhta, H., Kauppila, J., Isohookana, J., Haapasaari, K., Parkkila, S., Saarnio, J., Lehenkari, P., Karttunen, T. (2018) Weak HIF-1alpha expression indicates poor prognosis in resectable pancreatic ductal adenocarcinoma. World Journal of Surgical Oncology, 16 (1), 127. doi:10.1186/s12957-018-1432-4

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

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Author: Leppänen, Joni1,2; Helminen, Olli1; Huhta, Heikki1;
Organizations: 1Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital
2Department of Pathology, University of Oulu
3Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet
4School of Medicine, University of Tampere
5Fimlab Ltd, Tampere University Hospital
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 7.5 MB)
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Language: English
Published: Springer Nature, 2018
Publish Date: 2018-09-13


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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Series: World journal of surgical oncology
ISSN: 1477-7819
ISSN-E: 1477-7819
ISSN-L: 1477-7819
Volume: 16
Article number: 127
DOI: 10.1186/s12957-018-1432-4
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by grants from the Finnish Cultural Foundation (J.L), Finnish Medical Foundation (J.L), Emil Aaltonen Foundation (J.L), Sigrid Juselius Foundation (J.H.K.), Mary and Georg C Ehrnroot Foundation (J.H.K.), Thelma Mäkikyrö Foundation (J.H.K.), Orion Research Foundation (J.H.K.), and Päivikki and Sakari Sohlberg Foundation (J.L).
Dataset Reference: Additional files
Copyright information: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.