Pathology – Research and Practice 210 (2014) 105–110 Contents lists available at ScienceDirect Pathology – Research and Practice j ourna l h om epage: www.elsevier.com/locate/prp Original Article 14-3-3 gene expression exerts isoform-dependent functions in sinonasal pathophysiology Agapi Kataki a , Leonidas Alevizos a,∗ , Andreas Lazaris b , Georgia Glustianou c , Anastasia Derventzi a , Evagelos Giotakis d , Manousos Konstadoulakis a , Ioannis Yiotakis d a Laboratory of Surgical Research, 1st Department of Propaedeutic Surgery, University of Athens Hippocration Hospital, 114 Queen’s Sofia Avenue, 11527 Greece b Department of Pathology, Medical School, University of Athens, 75 Mikras Asias Street, Goudi, 11527 Athens, Greece c Histopathological Diagnosis, Soutsou 5, 11527, Athens, Greece d 1st Department of Otolaryngology, University of Athens, Hippocration Hospital of Athens, 114 Queen’s Sofia Avenue, 11527, Greece a r t i c l e i n f o Article history: Received 22 January 2013 Received in revised form 8 August 2013 Accepted 22 October 2013 Keywords: 14-3-3 isoforms Inverted papilloma Nasal polyps Proliferation Inflammation a b s t r a c t The expression profiles of 14-3-3 and  isoforms, known to exert both oncogenic and antiapoptotic effects, were assessed in different entities of nasal pathophysiology. Flow cytometry and immunohistochemistry were used on paraffin-embedded sections of 51 inverted papillomas (IP), 26 nasal polyps (NP), 9 polyps with IP (NPIP) and 10 specimens of normal epithelium (NE). 14-3-3 expression was significantly upregulated in IP as compared with both NP (p = 0.015) and NE (p = 0.002). 14-3-3 was also increased in NPIP as compared with NE (p = 0.008). 14-3-3 cytoplasmic staining was more pronounced in basal cells of the respiratory epithelium although serous glands and the vascular system were often positive as well. High 14-3-3 immunopositivity in IP patients concurred with increased proliferative activity shown by PCNA immunostaining (p = 0.04). Expression of 14-3-3 was also found increased in IP and NPIP patients, compared to NP (p = 0.005, p = 0.002 respectively) and NE (p = 0.004 and p = 0.001 respectively). 14-3-3 cytoplasmic immunopositivity was detected in columnar epithelium, particularly in basal and subluminal cells, whereas no immunoreactivity was observed in NP and NE. Our results demonstrate differential expression of 14-3-3 and  isoforms in sinonasal pathophysio- logy, supporting their implication, respectively, in the proliferative and inflammatory process engaged in the formation of IP. © 2013 Elsevier GmbH. All rights reserved. Introduction Inverted papillomas (IP) are relatively uncommon benign tumors of the nasal and paranasal sinus epithelium that occur more often in men than in women [1–4]. IP originate from the Schneide- rian membrane and are characterized by extensive invaginations of the hyperplastic epithelium into the underlying stroma [5]. IP show an increased tendency to recurrence and malignant transforma- tion, and are thus associated with sinus cancer [6,7]. Bacterial and viral infections, chronic inflammatory conditions, allergies, tobacco and occupational exposures have been implicated in their etiology though their mechanisms of growth and malignant transformation are not as yet fully understood [8]. ∗ Corresponding author. Tel.: +30 2132088569; fax: +30 2107707574. E-mail addresses: leonalevizos@gmail.com, agapimayo@yahoo.com (L. Alevizos). Sinonasal polyps with epithelial hyperplasia are the most com- mon precursors of Schneiderian papillomas. NPs are abnormal lesions associated with chronic inflammation of nasal and sinus mucous membranes showing no predisposition to age or sex. Eosinophils and basement membrane thickening characterize NPs, while there is no expansive inversion of the often hyperplastic epithelium into the underlying stroma. Unlike polyps in other parts of the body, they are always benign. Sinusitis, allergy, vasomotor rhinitis, infectious rhinosinusitis and asthma are factors contribut- ing to NP growth [9]. Cell proliferation and apoptosis are known as the major causative mechanisms in abnormal lesions. Several studies have investigated epithelial proliferation and apoptotic indicators in both NP and IP. Increased epithelial cell proliferation has been indi- cated as the main factor involved in the development of NP and IP [10–13]. 14-3-3 proteins comprise a large family of small, acidic and highly conserved polypeptides found in all eukaryotic species 0344-0338/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.prp.2013.10.006