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

• Published in: Oncotarget Vol. 8; no. 17; pp. 28650 - 28659
• Main Authors: Lodewijk, Lutske, van Diest, Paul, van der Groep, Petra, Ter Hoeve, Natalie, Schepers, Abbey, Morreau, Johannes, Bonenkamp, Johannes, van Engen-van Grunsven, Adriana, Kruijff, Schelto, van Hemel, Bettien, Links, Thera, Nieveen van Dijkum, Els, van Eeden, Susanne, Valk, Gerlof, Borel Rinkes, Inne, Vriens, Menno
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 25-04-2017
• Subjects: Adult; Animals; Biomarkers, Tumor - metabolism; Carbonic Anhydrase IX - genetics; Carbonic Anhydrase IX - metabolism; Carcinoma, Neuroendocrine - diagnosis; Carcinoma, Neuroendocrine - mortality; Female; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Male; Mice; Middle Aged; Neoplasm Staging; Netherlands; Predictive Value of Tests; Prognosis; Research Paper; Survival Analysis; Thyroid Neoplasms - diagnosis; Thyroid Neoplasms - mortality; Vascular Endothelial Growth Factor A - metabolism; medullary thyroid cancer; hypoxia inducible factor 1 alpha; immunohistochemistry; tissue microarray; oncology
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15622

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