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Pathology & Oncology Research

, Volume 24, Issue 2, pp 289–296 | Cite as

Expression of Hypoxia-Associated Protein HIF-1α in Follicular Thyroid Cancer is Associated with Distant Metastasis

  • Aumayr Klaus
  • Osmen Fathi
  • Traub-Weidinger Tatjana
  • Niederle Bruno
  • Koperek OskarEmail author
Original Article

Abstract

Follicular thyroid carcinomas (FTCs) are the second most common malignant neoplasia of the thyroid and in general its prognosis is quite favorable. However, the occurrence of metastases or non-responsiveness to radioiodine therapy worsens the prognosis considerably. We evaluated immunohistochemically the expression of hypoxia-associated proteins by hypoxia-induced factor 1α (HIF-1α), the stroma-remodeling marker Tenascin C, as well as markers for the epithelial-mesenchymal transition (EMT), namely E-cadherin and slug in a series of 59 sporadic FTCs. In addition, various clinicopathologic parameters were assessed like TNM-staging, age, tumor size as well as tumor characteristics like desmoplasia, necrosis, and calcification. Overexpression of HIF-1α was seen in 29 of 59 tumors (49.2%) including 21 (35.6%) FTC with strong expression of tumor cell groups. HIF-1α correlated significantly with metastasis (p < 0.001; Mann-Whitney U test), degree of desmoplasia (p = 0.042, Kruskal-Wallis test), tenascin C expression (p = 0.042, Kruskal-Wallis test), calcification (p < 0.025, Kruskal–Wallis test), necrosis (p = 0.002), age (p = 0.011, Kruskal-Wallis test) and tumor stage UICC (p = 0.022, Kruskal-Wallis test). Furthermore, metastasis was associated with the degree of desmoplasia (p = 0.014; Fisher’s exact test), calcification (p = 0.008, Fisher’s exact test), necrosis (p = 0.042, Fisher’s exact test), tumor size (p = 0.015, Mann-Whitney U test), and age (p = 0.001, Mann-Whitney U test). In a Cox proportional hazards model, only metastasis remained as an independent risk factor for overall survival (hazard rate: 10.2 [95% CI, 02.19 to 47.26]; p = 0.003). Our data suggest that HIF-1α plays a critical role in the remodeling of the extracellular matrix as well as metastasizing process of follicular thyroid carcinoma and targeting hypoxia-associated and -regulated proteins may be considered as potential targets for personalized medicine.

Keywords

HIF-1α Hypoxia-associated proteins Tenascin Follicular thyroid cancer Desmoplastic stroma reaction Metastasis 

Notes

Compliance with Ethical Standards

Funding

This study was supported by the Medical Scientific Fund of the Mayor of the City of Vienna (project # 10069).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Aumayr Klaus
    • 1
  • Osmen Fathi
    • 1
  • Traub-Weidinger Tatjana
    • 2
  • Niederle Bruno
    • 3
  • Koperek Oskar
    • 1
    Email author
  1. 1.Clinical Institute of PathologyMedical University of ViennaViennaAustria
  2. 2.Division of Nuclear Medicine, Department of RadiologyMedical University of ViennaViennaAustria
  3. 3.Section of Endocrine Surgery, Division of General Surgery, Department of SurgeryMedical University of ViennaViennaAustria

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