Presence of pepsin in laryngeal tissue and saliva in benign and malignant neoplasms.

Željko Zubčić,Vjeran Bogović,Hrvoje Mihalj,Stjepan Grga Milanković,Tihana Mendeš,Andrijana Včeva

doi:10.1042/bsr20200216

Abstract

Objectives: The current study was performed to determine the presence of pepsin in saliva and laryngeal tissue among participants with benign and malignant laryngeal neoplasms.Study design: Case–control study included three groups of patients with: (1) benign laryngeal neoplasms, (2) malignant laryngeal neoplasms and (3) control subjects without symptoms or signs of laryngopharyngeal reflux (LPR).Methods: Eighty-one voluntary participants were included into study. They were recruited from a group of patients with histologically proven benign and malignant laryngeal neoplasms and in case of control subjects among patients with nasal septum deformation without symptoms of LPR.Morning saliva samples were collected preoperatively. Tumor biopsies were collected by directoscopy of larynx and the control samples from interarytenoid unit of larynx. All samples were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA) and Immunohistochemistry.Results: Pepsin was found in all samples of saliva and tissue biopsies in groups with malignant and benign neoplasms. The highest concentration of pepsin was found in a group of patients with malignant laryngeal neoplasms. Patients with benign laryngeal neoplasms had lower concentrations and the control subjects presented with the lowest concentration of pepsin measured from their saliva. Differences were not statistically significant. Immunohistochemical (IHC) analysis showed the largest number of high positive samples in the group of malignant lesions.Conclusion: These results suggest that pepsin and LPR can contribute to the development of benign and malignant laryngeal neoplasms. Further prospective studies, with far more patients, are necessary to prove the role of pepsin in multifactorial etiology of laryngeal neoplasms.

Highlights

Various tumors develop in the larynx due to different origins, various tissue histogenesis and mucosal features
In the group with malignant lesions, the only diagnosis was planocellular carcinoma (PCC) 25 (45%), while other diagnoses occurred in the group with benign lesions (Fisher’s exact test, P
The results indicated a higher concentration of pepsin in saliva in the group with benign and malignant changes in the larynx than in healthy individuals, which could be explained by a higher incidence of laryngopharyngeal reflux (LPR) in the two study groups

Summary

Introduction

Various tumors develop in the larynx due to different origins, various tissue histogenesis and mucosal features. Regarding their biological behavior, tumors are divided into benign and malignant, which has high clinical significance. The latest hypothesis of etiology benign and malignant lesions in the larynx, as well as many other respiratory diseases, is based on laryngopharyngeal reflux (LPR) and pepsin activity. Still there are no established data for LPR as a definitive risk factor for benign and malignant lesions. Laryngeal tissues are essentially resistant to damage at pH 4.0, but are damaged when pepsin is present This suggests that in LPR, pH 4.0 or above, refluxate would only be damaging if it contained pepsin [4]. PH metric studies showed that these patients have LPR [6]

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