ArticleVirchows Archiv : an international journal of pathology2013
In papillary thyroid carcinoma, TIMP-1 expression correlates with BRAF (V600E) mutation status and together with hypoxia-related proteins predicts aggressive behavior.
Article in Virchows Archiv : an international journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 24 citations in OpenAlex.
- Current Studies on the Hypoxic Tumor Microenvironment in Thyroid Cancer: From Molecular Mechanisms to Clinical Therapeutic Perspectives.Biomedicines · 2026Review
- Environmental Exposure to Bisphenol A Enhances Invasiveness in Papillary Thyroid Cancer.International journal of molecular sciences · 2025Article
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- Urinary Exosomal Tissue TIMP and Angiopoietin-1 Are Preoperative Novel Biomarkers of Well-Differentiated Thyroid Cancer.Biomedicines · 2022Article
- Article
- Extracellular Vesicles as Signal Carriers in Malignant Thyroid Tumors?International journal of molecular sciences · 2022Article
- Identifying key genes of classic papillary thyroid cancer in women aged more than 55 years old using bioinformatics analysis.Frontiers in endocrinology · 2022Article
- Review
- Thyroid Cancer Stem-Like Cells: From Microenvironmental Niches to Therapeutic Strategies.Journal of clinical medicine · 2021Review
- Hif-1α Inhibitors Could Successfully Inhibit the Progression of Differentiated Thyroid Cancer in Vitro.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Immunomodulatory Effects of Vitamin D in Thyroid Diseases.Nutrients · 2020Review
- Cancer Stem Cells in Thyroid Tumors: From the Origin to Metastasis.Frontiers in endocrinology · 2020Review
- Validation of molecular biomarkers for preoperative diagnostics of human papillary thyroid carcinoma in fine needle aspirates.Gland surgery · 2019Article
- Article
- Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis.Oncotarget · 2015Article
- Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma.International journal of clinical and experimental pathology · 2014Article
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13 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
BRAF (V600E) causes upregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1), which promotes cell invasion in papillary thyroid carcinoma (PTC). Hypoxia-inducible factor-1α (HIF- α) is regulated by hypoxia and also by the BRAF-mediated signaling pathway in PTC. We assessed the association of expression of TIMP-1, HIF-1α, and hypoxia-inducible carbonic anhydrase IX (CAIX) and XII (CAXII) with clinical parameters in PTC. TPC-1/BRAF (WT) wild-type and BcPAP/BRAF (V600E) -mutated PTC cell lines were selected to study the effects of the BRAF (V600E) mutation and hypoxia on expression in vitro of TIMP-1, CAIX, and CAXII proteins by immunoblotting. Higher expression of all proteins was detected in BcPAP cells exposed to hypoxia. Tissue microarray immunohistochemistry analysis was performed to study protein expression in 114 BRAF-genotyped PTC samples. Expression data on tumor tissue were compared with clinicopathological variables. TIMP-1 expression had a sensitivity of 87 % and a specificity of 83 % in identifying a BRAF mutation (P < 0.001) and was associated with pT stage (P = 0.001), pN stage (P = 0.02), and multifocality (P = 0.03). HIF-1α expression correlated with pT stage (P = 0.05). CAIX expression was associated with pN stage (P = 0.02), and both CAIX (P = 0.004) and CAXII (P = 0.05) were strongly associated with vascular invasion. We conclude that TIMP-1 protein expression is a reliable surrogate marker for BRAF-mutated status in PTC. TIMP-1 and hypoxia-regulated proteins are promising as predictors of aggressiveness in PTC and warrant further investigation as new therapeutic targets for the treatment of highly aggressive forms of PTC.
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