{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:31:04Z","timestamp":1781566264817,"version":"3.54.5"},"reference-count":24,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2016,7,9]],"date-time":"2016-07-09T00:00:00Z","timestamp":1468022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tenascin C expression correlates with tumor grade and indicates worse prognosis in several tumors. Epidermal growth factor receptor (EGFR) plays an important role in driving proliferation in many tumors. Loss of E-cadherin function is associated with tumor invasion and metastasis. Thyroid transcription factor-1 (TTF-1) is involved in rearranged during transfection (RET) transcription in Hirschsprung\u2019s disease. Tenascin C, EGFR, E-cadherin, TTF-1-expression, and their correlations with RET mutation status were investigated in 30 patients with medullary thyroid carcinoma (MTC) (n = 26) or C-cell hyperplasia (n = 4). Tenascin C was found in all, EGFR in 4\/26, E-cadherin in 23\/26, and TTF-1 in 25\/26 MTC. Tenascin C correlated significantly with tumor proliferation (overall, r = 0.61, p &lt; 0.005; RET-mutated, r = 0.81, p &lt; 0.01). E-cadherin showed weak correlation, whereas EGFR and TTF-1 showed no significant correlation with tumor proliferation. EGFR, E-cadherin, and TTF-1 showed weak correlation with proliferation of RET-mutated tumors. Correlation between TTF-1 and tenascin C, E-cadherin, and EGFR was r = \u22120.10, 0.37, and 0.21, respectively. In conclusion, MTC express tenascin C, E-cadherin, and TTF-1. Tenascin C correlates significantly with tumor proliferation, especially in RET-mutated tumors. EGFR is low, and tumors expressing EGFR do not exhibit higher proliferation. TTF-1 does not correlate with RET mutation status and has a weak correlation with tenascin C, E-cadherin, and EGFR expression.<\/jats:p>","DOI":"10.3390\/ijms17071093","type":"journal-article","created":{"date-parts":[[2016,7,11]],"date-time":"2016-07-11T09:47:19Z","timestamp":1468230439000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Expression of Tenascin C, EGFR, E-Cadherin, and TTF-1 in Medullary Thyroid Carcinoma and the Correlation with RET Mutation Status"],"prefix":"10.3390","volume":"17","author":[{"given":"Florian","family":"Steiner","sequence":"first","affiliation":[{"name":"Department of Pathology, Paracelsus Medical University Salzburg, M\u00fcllner Hauptstrasse 48, A-5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Hauser-Kronberger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Paracelsus Medical University Salzburg, M\u00fcllner Hauptstrasse 48, A-5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundula","family":"Rendl","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrinology, Paracelsus Medical University Salzburg, M\u00fcllner Hauptstrasse 48, A-5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrinology, Paracelsus Medical University Salzburg, M\u00fcllner Hauptstrasse 48, A-5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Pirich","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Endocrinology, Paracelsus Medical University Salzburg, M\u00fcllner Hauptstrasse 48, A-5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,7,9]]},"reference":[{"key":"ref_1","unstructured":"DeVita, V.T., Jr., Hellman, S., and Rosenberg, S.A. (2001). Cancer: Principles and Practice of Oncology, Lippincott. [6th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/bies.950190506","article-title":"RET in human development and oncogenesis","volume":"19","author":"Edery","year":"1997","journal-title":"Bioessays"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ng0595-35","article-title":"Loss of function effect of RET mutations causing Hirschsprung disease","volume":"10","author":"Pasini","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/(SICI)1096-9896(199708)182:4<421::AID-PATH886>3.0.CO;2-U","article-title":"Co-expression of tenascin and fibronectin in epithelial and stromal cells of benign lesions and ductal carcinomas in the human breast","volume":"182","author":"Yoshida","year":"1997","journal-title":"J. Pathol."},{"key":"ref_5","first-page":"2796","article-title":"Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody","volume":"43","author":"Bourdon","year":"1983","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/ijc.10233","article-title":"Clinical impact and functional aspects of tenascin-C expression during glioma progression","volume":"98","author":"Mueller","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00428-009-0786-y","article-title":"Tenascin C in medullary thyroid microcarcinoma and C-cell hyperplasia","volume":"455","author":"Koperek","year":"2009","journal-title":"Virchows Arch."},{"key":"ref_8","first-page":"3140","article-title":"Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas","volume":"55","author":"Wikstrand","year":"1995","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1677\/ERC-08-0304","article-title":"Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis","volume":"17","author":"Pallares","year":"2010","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4183","DOI":"10.1158\/0008-5472.CAN-08-0413","article-title":"RET\/PTC-induced cell growth is mediated in part by epidermal growth factor receptor (EGFR) activation: Evidence for molecular and functional interactions between RET and EGFR","volume":"68","author":"Croyle","year":"2008","journal-title":"Cancer Res."},{"key":"ref_11","first-page":"2185","article-title":"Expression of E- and P-cadherin in gastric carcinomas","volume":"51","author":"Shimoyama","year":"1991","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0092-8674(91)90143-M","article-title":"Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role","volume":"66","author":"Vleminckx","year":"1991","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/jso.1031","article-title":"Clinical significance of E-cadherin expression in thyroid neoplasms","volume":"76","author":"Naito","year":"2001","journal-title":"J. Surg. Oncol."},{"key":"ref_14","first-page":"576","article-title":"Cell-type-specific expression of the rat thyroperoxidase promoter indicates common mechanisms for thyroid-specific gene expression","volume":"12","author":"Price","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1002\/j.1460-2075.1989.tb08391.x","article-title":"A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter","volume":"8","author":"Civitareale","year":"1989","journal-title":"EMBO J."},{"key":"ref_16","first-page":"4744","article-title":"Expression of thyroid-specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasms","volume":"54","author":"Fabbro","year":"1994","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0046-8177(00)80255-5","article-title":"Expression of thyroid transcription factor-1 (TTF-1) in human C cells and medullary thyroid carcinomas","volume":"31","author":"Katoh","year":"2000","journal-title":"Hum. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7410","DOI":"10.1128\/MCB.18.12.7410","article-title":"Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells","volume":"18","author":"Suzuki","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhu, J., Garcia-Barcelo, M.M., Tam, P.K.H., and Lui, V.C.H. (2011). HOXB5 cooperates with NKX2\u20131 in the transcription of human RET. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020815"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1038\/sj.bjc.6601453","article-title":"The Ki67 index a prognostic marker in medullary thyroid carcinoma","volume":"89","author":"Tisell","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/ERC-09-0292","article-title":"The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells","volume":"18","author":"Vitagliano","year":"2011","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_22","first-page":"1035","article-title":"Tenascin expression in cancer cells and stroma of human breast cancer and its prognostic significance","volume":"1","author":"Ishihara","year":"1995","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1089\/thy.2008.0403","article-title":"Medullary thyroid cancer: Management guidelines of the American Thyroid Association","volume":"19","author":"Kloos","year":"2009","journal-title":"Thyroid"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/hmg\/ddi015","article-title":"TTF-1 and RET promoter SNPs: Regulation of RET transcription in Hirschsprung\u2019s disease","volume":"14","author":"Ganster","year":"2005","journal-title":"Hum. Mol. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/7\/1093\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:25:46Z","timestamp":1760210746000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/7\/1093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,9]]},"references-count":24,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7]]}},"alternative-id":["ijms17071093"],"URL":"https:\/\/doi.org\/10.3390\/ijms17071093","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,9]]}}}