Abstract
BackgroundMedullary 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.MethodsAll 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.ResultsThe 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).ConclusionExpression of HIF-1α is strongly correlated with adverse prognosis of MTC. This could open up new ways for targeted systemic therapy of MTC.
Highlights
Medullary thyroid cancer (MTC) accounts for 4% of all thyroid cancers and, in contrast to other forms of thyroid cancer, it arises from the parafollicular C-cells
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)
Even within the group of patients with TNMstage 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)
Summary
Medullary thyroid cancer (MTC) accounts for 4% of all thyroid cancers and, in contrast to other forms of thyroid cancer, it arises from the parafollicular C-cells It occurs either as a sporadic disease or in a hereditary context as a manifestation of the endocrine tumor syndrome Multiple Endocrine Neoplasia type 2 (MEN2) (20-25%) [1]. About 45% of all patients present with advanced disease (stage III-IV), which has a 10-year survival rate of 71% and 21%, respectively [2]. Clinical variables such as age, extent of the primary tumor, lymph node metastases and distant metastases have been identified as prognostic factors [2]. Our aim was to evaluate the prognostic value of HIF-1α in patients with MTC
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