Contents lists available at ScienceDirect Tissue and Cell journal homepage: www.elsevier.com/locate/tice The prognostic value of sex hormone receptors expression in laryngeal carcinoma Aliaa Atef a , Mohamed A. El-Rashidy a , Saad Elzayat b , Ahmed M. Kabel c,d, ⁎ a Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt b Otorhinolaryngology Department, Kafrelsheikh University, Kafrelsheikh, Egypt c Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt d Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia ARTICLE INFO Keywords: Larynx Carcinoma Sex hormones Receptors ABSTRACT Laryngeal cancer was identified as the second most common respiratory system malignancy with squamous cell carcinoma being the most common malignant tumor of the larynx. Larynx being a secondary sex organ showing physiological changes during puberty, raises inquiry about the relationship between sex hormones receptors as estrogen receptors (ER), progesterone receptors (PR), androgen receptors (AR) and the development of laryngeal carcinoma. This study was carried out in cancer tissue samples from 50 patients with laryngeal squamous cell carcinoma. Immunohistochemical staining using ER-β, PR, and AR was carried out. The immunohistochemical expression of ER-β, PR and AR was positive in 56%, 50% and 64% of cases respectively. ER-β, and PR expression were significantly higher in poorly differentiated cases and cases with lymphatic invasion while AR expression was significantly lower in poorly differentiated cases and with lymphatic invasion. In conclusion, ER-β and PR may be considered as markers for poor biological behavior of laryngeal carcinoma. 1. Introduction Laryngeal cancer was considered as the second most common ma- lignancy of the respiratory system after bronchogenic carcinoma. Squamous cell carcinoma is the most common malignant tumor of the larynx representing about 90% of laryngeal cancers. Males are more frequently affected than females mostly in the 5 th to the 7 th decades. The most significant predisposing factors are smoking and alcoholism (Fletcher, 2013; Kabel and Elkhoely, 2016). Larynx being a secondary sex organ showing physiological changes during puberty, raises inquiry about the relation between sex hormones receptors as Estrogen re- ceptors (ER), Progesterone receptors (PR), Androgen receptors (AR) and the development of laryngeal carcinoma suggesting that laryngeal carcinoma may be a sex hormone-dependent tumor same as prostatic and breast carcinoma with the possibility of their treatment using anti- androgen and antiestrogen therapy (Hagedorn and Nerlich, 2002). The common manifestations of laryngeal cancer can be hoarseness or change voice, pain, hemoptysis, stridor or airway obstruction in advanced cases. Glottic types are more common than supraglottic and subglottic ones (Fried and Gopal, 1996). Estrogen and progesterone are hormones with nuclear receptors acting as ligand-dependent transcription factors. Before this binding, ERs and PRs are inactive in the cytoplasm bound to heat shock proteins. Ligand binding stops the inhibitory heat shock proteins, and ERs and PRs move to the nucleus and binds to DNA to be involved in the reg- ulation of the cell cycle, cell adhesion and differentiation (Goulioumis et al., 2009). The role of estrogen in carcinogenesis is controversial. The hormone acts often as a cancer promoter in breast carcinomas, while in some other types of cancers, it can inhibit cancer cells invasion (Yager, 2014). Estrogen receptors may have a role in the pathogenesis of the gastro- intestinal tumors particularly in esophageal carcinoma which is the closest part of the gastrointestinal tract to the larynx (Nie et al., 2018; Yang et al., 2012). This can be attributed to the presence of two types of estrogen receptors; estrogen receptor α (ER- α) and β (ER-ß) (Liu et al., 2002; Helguero et al., 2008). The role of ER-ß in laryngeal cancer is unknown (Jarvinen et al., 2000; Konstantinopoulos et al., 2003; Lazennec, 2006). Dong et al. (2013) reported that downregulation of ERα and upregulation of ERβ may indicate unfavorable prognosis of esophageal squamous cell carcinoma. Many previous studies discussed the different susceptibilities of the tumor cells to sex hormones. In a small number of studies, ER and PR proteins were identified biochemically, but none of these studies clearly proved that cancer cells themselves express those hormone receptors https://doi.org/10.1016/j.tice.2019.02.007 Received 6 July 2018; Received in revised form 20 February 2019; Accepted 21 February 2019 ⁎ Corresponding author at: El-Geish Street, Faculty of Medicine, Tanta University, Department of Pharmacology, Tanta, 31527, Egypt. E-mail address: ahmed.kabal@med.tanta.edu.eg (A.M. Kabel). Tissue and Cell 57 (2019) 84–89 Available online 22 February 2019 0040-8166/ © 2019 Elsevier Ltd. All rights reserved. T