Research ArticlesNuclear EGFR Expression Is Associated With Poor Survival in Laryngeal CarcinomaMarijić, Blažen MD*,†; Braut, Tamara MD, PhD*,†; Babarović, Emina MD, PhD‡; Krstulja, Mira MD, PhD‡; Maržić, Diana MD†,§; Avirović, Manuela MD, PhD‡,∥; Kujundžić, Milodar MD, PhD*,†; Hadžisejdić, Ita MD, PhD‡,∥ Author Information *Department of Otorhinolaryngology and Head and Neck Surgery ∥Clinical Department of Pathology and Cytology §Department of Audiology and Phoniatrics, Clinical Hospital Centre Rijeka Departments of †Otorhinolaryngology ‡Pathology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia Supported by the project of University of Rijeka, Croatia (grant number uniri-biomed-18-121). The authors declare no conflict of interest. Reprints: Ita Hadžisejdić, MD, PhD, Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia (e-mail: [email protected]). Applied Immunohistochemistry & Molecular Morphology: September 2021 - Volume 29 - Issue 8 - p 576-584 doi: 10.1097/PAI.0000000000000932 Buy SDC Metrics Abstract The membrane EGFR (mEGFR) protein overexpression in the head and neck squamous cell carcinoma (SCC) is considered to cause increased EGFR activity which adds to tumorigenicity and therapy resistance. The mEGFR upon stimulation can translocate to the nucleus nuclear EGFR (nEGFR) where it has been associated with poor prognosis and worse survival in many cancers. The relevance of differentially located EGFR proteins in laryngeal lesions has not been studied enough and remains unclear. Aim of our study was to examine nEGFR and mEGFR protein expression as well as EGFR gene status and cell cycle proliferation markers in the laryngeal polyps, dysplasia, and SCC using immunohistochemistry and in situ hybridization. There was significantly higher frequency of strong nEGFR between SCC, dysplasia, and polyps (P<0.0001), and strong mEGFR in the SCC and laryngeal dysplasia comparing to polyps (P<0.0001). Gene amplification was confirmed only in relatively small number of SCC but not in non-neoplastic lesions. In dysplasia the statistically significant positive correlations between nEGFR, and Ki-67 (P=0.029), p53 (P=0.001), and cyclin D1 (P=0.031) were found. nEGFR and mEGFR expression showed statistically significant inverse correlation in the SCC (P=0.004) as well as nEGFR and cyclin D1 (P=0.032). Univariate statistical analysis showed statistically significant correlation between strong nEGFR protein expression and worse overall survival in laryngeal SCC, alone or in coexpression with strong cyclin D1 and high Ki-67 (P=0.025, P=0.046, P=0.043, respectively). Our data show that nEGFR cellular localization might influence biology of the laryngeal carcinogenesis and is indicator of poor survival. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.