Pathology oncology research: POR | |
Expression of Hypoxia-Associated Protein HIF-1α in Follicular Thyroid Cancer is Associated with Distant Metastasis | |
Aumayr Klaus1  | |
[1] Medical University of Vienna | |
关键词: HIF-1α; Hypoxia-associated proteins; Tenascin; Follicular thyroid cancer; Desmoplastic stroma reaction; Metastasis; | |
DOI : 10.1007/s12253-017-0232-4 | |
学科分类:生理学与病理学 | |
来源: Springer | |
【 摘 要 】
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, KruskalâWallis 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; Fisherâs exact test), calcification (p = 0.008, Fisherâs exact test), necrosis (p = 0.042, Fisherâs 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.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
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RO201910258684700ZK.pdf | 910KB | download |