Oncotarget

Research Papers:

Expression of HIF-1α in medullary thyroid cancer identifies a subgroup with poor prognosis

Lutske Lodewijk, Paul van Diest, Petra van der Groep, Natalie ter Hoeve, Abbey Schepers, Johannes Morreau, Johannes Bonenkamp, Adriana van Engen - van Grunsven, Schelto Kruijff, Bettien van Hemel, Thera Links, Els Nieveen van Dijkum, Susanne van Eeden, Gerlof Valk, Inne Borel Rinkes and Menno Vriens _

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Oncotarget. 2017; 8:28650-28659. https://doi.org/10.18632/oncotarget.15622

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Abstract

Lutske Lodewijk1, Paul van Diest2, Petra van der Groep2, Natalie ter Hoeve2, Abbey Schepers4, Johannes Morreau5, Johannes Bonenkamp6, Adriana van Engen - van Grunsven7, Schelto Kruijff8, Bettien van Hemel9, Thera Links10, Els Nieveen van Dijkum11, Susanne van Eeden12, Gerlof Valk3, Inne Borel Rinkes1, Menno Vriens1

1University Medical Center Utrecht, Department of Surgery, 3584CX Utrecht, The Netherlands

2University Medical Center Utrecht, Department of Pathology, 3584CX Utrecht, The Netherlands

3University Medical Center Utrecht, Department of Endocrine Oncology, 3584CX Utrecht, The Netherlands

4Leiden University Medical Center, Department of Surgery, 2333ZA Leiden, The Netherlands

5Leiden University Medical Center, Department of Pathology, 2333ZA Leiden, The Netherlands

6Radboud University Medical Center, Department of Surgery, Nijmegen 6525GA, The Netherlands

7Radboud University Medical Center, Department of Pathology, Nijmegen 6525GA, The Netherlands

8University Medical Center Groningen, Department of Surgery, 9700 RB, Groningen, The Netherlands

9University Medical Center Groningen, Department of Pathology, 9700 RB, Groningen, The Netherlands

10University Medical Center Groningen, Department of Internal Medicine, 9700 RB, Groningen, The Netherlands

11Academic Medical Center Amsterdam, Department of Surgery, 1105 AZ, Amsterdam, The Netherlands

12Academic Medical Center Amsterdam, Department of Pathology, 1105 AZ, Amsterdam, The Netherlands

Correspondence to:

Menno Vriens, email: mvriens@umcutrecht.nl

Keywords: medullary thyroid cancer, hypoxia inducible factor 1 alpha, immunohistochemistry, tissue microarray, oncology

Received: October 12, 2016    Accepted: January 24, 2017    Published: February 22, 2017

ABSTRACT

Background: Medullary thyroid cancer (MTC) comprises only 4% of all thyroid cancers and originates from the parafollicular C-cells. HIF-1α expression has been implied as an indicator of worse prognosis in various solid tumors. However, whether expression of HIF-1α is a prognosticator in MTC remained unclear. Our aim was to evaluate the prognostic value of HIF-1α in patients with MTC.

Methods: All patients with MTC who were operated on between 1988 and 2014 in five tertiary referral centers in The Netherlands were included. A tissue microarray was constructed in which 111 primary tumors could be analyzed for expression of HIF-1α, CAIX, Glut-1, VEGF and CD31 and correlated with clinicopathologic variables and survival.

Results: The mean age of patients was 46.3 years (SD 15.6), 59 (53.2%) were male. Of the 111 primary tumors, 49 (44.1%) were HIF-1α negative and 62 (55.9%) were HIF-1α positive. Positive HIF-1α expression was an independent negative indicator for progression free survival (PFS) in multivariate cox regression analysis (HR 3.1; 95% CI 1.3 – 7.3). Five-years survival decreased from 94.0% to 65.9% for the HIF-1α positive group (p=0.007). Even within the group of patients with TNM-stage IV disease, HIF-1α positivity was associated with a worse prognosis, shown by a decrease in 5-years survival of 88.0% to 49.3% (p=0.020).

Conclusion: Expression of HIF-1α is strongly correlated with adverse prognosis of MTC. This could open up new ways for targeted systemic therapy of MTC.


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