{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:14:25Z","timestamp":1791897265346,"version":"4.3.4"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The aim of this study was to (i) determine IMP3 protein expression in benign and malignant laryngeal lesions, (ii) compare its expression to Ki-67, p53, cyclin D1, and (iii) finally, to examine the prognostic power of IMP3 in squamous cell carcinomas of the larynx (LSSC). Methods: IMP3 protein expression was evaluated in 145 patients, including 62 LSCC, 45 dysplasia (25 with low and 20 with high-grade dysplasia), and 38 benign lesions (vocal cord polyps and nodules). Results: IMP3 was significantly higher expressed in LSCC compared to dysplasia and benign lesions (p &lt; 0.001; p &lt; 0.001, respectively). Similarly, higher expression patterns were observed for Ki-67 and p53, whereas cyclin D1 was equally distributed in all three lesions. IMP3 (p = 0.04) and Ki-67 (p = 0.02) expressions were significantly linked to neck node positivity, and IMP3 overexpression to worse disease-specific survival (p = 0.027). Conclusion: Since IMP3 showed significantly higher expression in laryngeal carcinomas, but not in high- or low-grade dysplasia, it serves as a useful marker to differentiate between invasive and noninvasive lesions. Higher IMP3 expression represented a significantly worse prognosticator for clinical outcomes of patients with squamous cell carcinoma of the larynx.<\/jats:p>","DOI":"10.3390\/cancers13174306","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T09:27:57Z","timestamp":1629970077000},"page":"4306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["IMP3 Protein Overexpression Is Linked to Unfavorable Outcome in Laryngeal Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Diana","family":"Mar\u017ei\u0107","sequence":"first","affiliation":[{"name":"Department of Audiology and Phoniatrics, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia"},{"name":"Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6094-7114","authenticated-orcid":false,"given":"Bla\u017een","family":"Mariji\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Institute of Head and Neck Diseases, Evangelical Hospital, 1180 Vienna, Austria"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Braut","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1161-4871","authenticated-orcid":false,"given":"Stefan","family":"Janik","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Medical University Vienna, 1190 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Avirovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1800-3552","authenticated-orcid":false,"given":"Ita","family":"Had\u017eisejdi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6386-0444","authenticated-orcid":false,"given":"Filip","family":"Tudor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Radobuljac","sequence":"additional","affiliation":[{"name":"Department of Audiology and Phoniatrics, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miran","family":"\u010coklo","sequence":"additional","affiliation":[{"name":"Center for Applied Bioanthropology, Institute for Anthropological Research, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-1056","authenticated-orcid":false,"given":"Boban M.","family":"Erovic","sequence":"additional","affiliation":[{"name":"Institute of Head and Neck Diseases, Evangelical Hospital, 1180 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.20892\/j.issn.2095-3941.2016.0010","article-title":"Changing the paradigm: The potential for targeted therapy in laryngeal squamous cell carcinoma","volume":"13","author":"Ludwig","year":"2016","journal-title":"Cancer Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Faisal, M., Hartenbach, S., Schratter, A., Kostler, W.J., Kaufmann, H., Seemann, R., Lill, C., Hamzavi, S., Wutzl, A., and Erovic, B.M. (2020). Lymphoepithelial Carcinoma of Larynx and Hypopharynx: A Rare Clinicopathological Entity. Cancers, 12.","DOI":"10.3390\/cancers12092431"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Grasl, S., Schmid, E., Heiduschka, G., Brunner, M., Marijic, B., Grasl, M.C., Faisal, M., Erovic, B.M., and Janik, S. (2021). A New Classification System to Predict Functional Outcome after Laryngectomy and Laryngopharyngectomy. Cancers, 13.","DOI":"10.3390\/cancers13061474"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/coa.13353","article-title":"Post-laryngectomy adjuvant radiotherapy in patients with pharyngocutaneous fistulae: Treatment regimens, outcomes and complications in 67 patients","volume":"44","author":"Parzefall","year":"2019","journal-title":"Clin. Otolaryngol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E1515","DOI":"10.1002\/hed.24271","article-title":"Effect of postoperative use of diclofenac on pharyngocutaneous fistula development after primary total laryngopharyngectomy: Results of a single-center retrospective study","volume":"38","author":"Parzefall","year":"2016","journal-title":"Head Neck"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1002\/hed.26433","article-title":"Panendoscopy during follow-up in laryngeal carcinoma patients after radiotherapy","volume":"42","author":"Stanisz","year":"2020","journal-title":"Head Neck"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/coa.13468","article-title":"Lymph node ratio as a prognostic marker in advanced laryngeal and hypopharyngeal carcinoma after primary total laryngopharyngectomy","volume":"45","author":"Grasl","year":"2020","journal-title":"Clin. Otolaryngol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1091\/mbc.e12-05-0394","article-title":"An expanding role for cell biologists in drug discovery and pharmacology","volume":"23","author":"Sorger","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zahavi, D., and Weiner, L. (2020). Monoclonal Antibodies in Cancer Therapy. Antibodies, 9.","DOI":"10.3390\/antib9030034"},{"key":"ref_10","first-page":"7497","article-title":"Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma","volume":"15","author":"Kozakiewicz","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s40265-017-0734-0","article-title":"Targeted Therapy in Head and Neck Cancer: An Update on Current Clinical Developments in Epidermal Growth Factor Receptor-Targeted Therapy and Immunotherapies","volume":"77","author":"Moreira","year":"2017","journal-title":"Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.2147\/OTT.S128810","article-title":"Prognostic value of high IMP3 expression in solid tumors: A meta-analysis","volume":"10","author":"Chen","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0925-4773(99)00160-4","article-title":"Expression of the highly conserved RNA binding protein KOC in embryogenesis","volume":"88","author":"Pohl","year":"1999","journal-title":"Mech. Dev."},{"key":"ref_14","first-page":"3","article-title":"IMP3 overexpression occurs in various important cancer types and is linked to aggressive tumor features: A tissue microarray study on 8877 human cancers and normal tissues","volume":"39","author":"Burdelski","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1016\/j.humpath.2013.04.002","article-title":"Oncofetal protein IMP3: A new diagnostic biomarker for laryngeal carcinoma","volume":"44","author":"Chen","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1097\/PAI.0000000000000319","article-title":"IMP3 Immunoreactivity is More Sensitive than AMACR in Detecting Dysplastic Epithelium and Early Adenocarcinoma in Barrett Esophagus","volume":"25","author":"Gadara","year":"2017","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s12094-014-1216-4","article-title":"Expression and clinical significance of IMP3 in microdissected premalignant and malignant pancreatic lesions","volume":"17","author":"Wang","year":"2015","journal-title":"Clin. Transl. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.fertnstert.2013.02.002","article-title":"The oncofetal protein IMP3: A novel biomarker and triage tool for premalignant atypical endometriotic lesions","volume":"99","author":"Vercellini","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"30","DOI":"10.5152\/balkanmedj.2015.15547","article-title":"Imp3 expression in benign and malignant thyroid tumors and hyperplastic nodules","volume":"32","author":"Kulacoglu","year":"2015","journal-title":"Balkan Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152974","DOI":"10.1016\/j.prp.2020.152974","article-title":"The expression of ribonuclear protein IMP3 in laryngeal carcinogenesis","volume":"216","author":"Marzic","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Marijic, B., Braut, T., Babarovic, E., Krstulja, M., Marzic, D., Avirovic, M., Kujundzic, M., and Hadzisejdic, I. (2021). Nuclear EGFR Expression Is Associated with Poor Survival in Laryngeal Carcinoma. Appl. Immunohistochem. Mol. Morphol.","DOI":"10.1097\/PAI.0000000000000932"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.prp.2018.11.001","article-title":"Immunohistochemical analysis of vocal cord polyps applying markers of squamous cell carcinogenesis","volume":"215","author":"Braut","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1002\/hed.25871","article-title":"VEGFR-2 is downregulated in sestamibi-negative parathyroid adenomas","volume":"41","author":"Erovic","year":"2019","journal-title":"Head Neck"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/hed.23021","article-title":"Identification of novel target proteins in sebaceous gland carcinoma","volume":"35","author":"Erovic","year":"2013","journal-title":"Head Neck"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e23943","DOI":"10.1097\/MD.0000000000023943","article-title":"New insights into erythropoietin and erythropoietin receptor in laryngeal cancer tissue","volume":"100","author":"Vukelic","year":"2021","journal-title":"Medicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8142572","DOI":"10.1155\/2019\/8142572","article-title":"The Relevance of Assessing the Cell Proliferation Factor Ki-67 in Squamous Cell Carcinoma of the Larynx","volume":"2019","author":"Vukelic","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/PAP.0000000000000021","article-title":"Oncofetal protein IMP3, a new cancer biomarker","volume":"21","author":"Gong","year":"2014","journal-title":"Adv. Anat. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1038\/sj.onc.1201110","article-title":"Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein","volume":"14","author":"Lacher","year":"1997","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3389\/fcell.2019.00363","article-title":"IGF2BP3 from Physiology to Cancer: Novel Discoveries, Unsolved Issues, and Future Perspectives","volume":"7","author":"Mancarella","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_30","first-page":"e14413","article-title":"Expression of IMP3 in a retrospective cohort of melanomas with selective lymph node biopsy","volume":"33","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S1470-2045(06)70732-X","article-title":"Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: A retrospective study","volume":"7","author":"Jiang","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_32","first-page":"10269","article-title":"Insulin-like growth factor II mRNA binding protein 3 regulates proliferation, invasion and migration of neuroendocrine cancer cells","volume":"10","author":"Er","year":"2017","journal-title":"Int. J. Clin. Exp. Pathol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4306\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:52:40Z","timestamp":1760165560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,26]]},"references-count":32,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cancers13174306"],"URL":"https:\/\/doi.org\/10.3390\/cancers13174306","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,26]]}}}