Investigation of Pepsin in Laryngeal Squamous Cell Carcinoma Specimens

Yıl 2019, Cilt: 46 Sayı: 4, 657 - 665, 15.12.2019

Hamdi Tasli Burcu Eser Hakan Birkent Burak Asik Mustafa Gerek

https://doi.org/10.5798/dicletip.661237

Öz

Objective: Squamous cell carcinoma (SCC) composes 95% of the carcinoma of the larynx. One of the factor recognized in the past two decades as increasing the risk of SCC is laryngopharyngeal reflux (LPR). The role and mechanism of LPR in laryngeal cancer remain unclear. The aim of this study was to assess the presence of pepsin in laryngeal formalin-fixed, paraffin-embedded (FFPE) squamous cell carcinoma (SCC) specimens in order to test the hypothesis that LPR plays a role in the development of laryngeal SCC.
Method: A total of 29 pathology specimens of advanced-stage laryngeal cancer patients who had undergone total laryngectomy were evaluated. The specimens were confirmed histopathologically as SCC and maintained in paraffin blocks in the pathology department. The western blot (WB) or the enzyme-linked immunosorbent assay (ELISA) analyses were used to measure pepsin enzyme levels.
Results: According to the WB and ELISA analyses, there was no presence of the pepsin enzyme in any of the 29 formalin-fixed, paraffin-embedded (FFPE) laryngeal SCC specimens. However, pepsin was detected with both the WB and the ELISA tests in positive controls and fresh rat stomach specimen.
Conclusion: Pepsin was not present in any of the malignant laryngeal squamous cell carcinoma specimens in this study. Relationship between LPR and laryngeal SCC still remains unclear and further studies are needed to verify the role of pepsin and LPR in laryngeal SCC.

Anahtar Kelimeler

Laryngopharyngeal reflux; laryngeal carcinoma; pepsin; larynx

Kaynakça

• 1. Cann CI, Fried MP, Rothman KJ. Epidemiology of squamous cell cancer of the head and neck. Otolaryngol Clin North Am. 1985; 18: 367-88.
• 2. Landis SH, Murray T, Bolden S, et al. Cancer statistics, 1998. CA Cancer J Clin. 1998; 48: 6-29.
• 3. Berrino F. Survival of cancer patients in Europe: the EUROCARE-2 study. IARC Sci Publ. 1999; 151: 1-572.
• 4. Rothman KJ, Cann CI, Flanders D, et al. Epidemiology of laryngeal cancer. Epidemiologic reviews. 1980; 2: 195–209.
• 5. Copper MP, Smit CF, Stanojcic LD, et al. High incidence of laryngopharyngeal reflux in patients with head and neck cancer. Laryngoscope. 2000; 110: 1007–11.
• 6. Samuels TL, Johnston N. Pepsin as a Marker of Extraesophageal Reflux. Ann Otol Rhinol Laryngol. 2010; 119: 203-8.
• 7. Wassenaar E, Johnston N, Merati A, et al. Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication. Surg Endosc. 2011; 25: 3870-6.
• 8. Glanz H, Kleinsasser O. Chronic laryngitis and carcinoma. Arch Otorhinolaryngol. 1976; 212: 57-75.
• 9. Johnston N, Yan JC, Hoekzema CR, et al. Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells. Laryngoscope. 2012; 122: 1317-25.
• 10. Qadeer MA, Colabianchi N, Vaezi MF. Is GERD a risk factor for laryngeal cancer?. Laryngoscope. 2005; 115: 486–91.
• 11. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope. 2001; 111: 1313-7.
• 12. Tasli H, Eser B, Asik MB, et al. Does Pepsin Play a Role in Etiology of Laryngeal Nodules?. J Voice. 2018 May 11. pii: S0892-1997(18)30041-9.
• 13. Johnston N, Dettmar PW, Bishwokarma B, et al. Activity/stability of human pepsin: implications for reflux attributed laryngeal disease. Laryngoscope. 2007; 117: 1036–9.
• 14. Johnston N, Wells CW, Samuels TL, et al. Rationale for targeting pepsin in the treatment of reflux disease. Ann Otol Rhinol Laryngol. 2010; 119: 547–58.
• 15. Johnston N, Peter W. Dettmar PW, et al. Laryngopharyngeal reflux and GERD. Ann N Y Acad Sci. 2013; 1300: 71-9.
• 16. Coca-Pelaz A, Rodrigo JP, Takes RP, et al. Relationship between reflux and laryngeal cancer. Head Neck. 2013; 35: 1814-8.
• 17. Nilsson M, Chow WH, Lindblad M, et al. No association between gastroesophageal reflux and cancers of the larynx and pharynx. Cancer Epidemiol Biomarkers Prev. 2005; 14: 1194-7.
• 18. Francis DO, Maynard C, Weymuller EA, et al. Reevaluation of gastroesophageal reflux disease as a risk factor for laryngeal cancer. Laryngoscope. 2011; 121: 102-5.
• 19. Ozlugedik S, Yorulmaz I, Gokcan K. Is laryngopharyngeal reflux an important risk factor in the development of laryngeal carcinoma?. Eur Arch Otorhinolaryngol. 2006; 263: 339–43.
• 20. Geterud A, Bove M, Ruth M. Hypopharyngeal acid exposure: an independent risk factor for laryngeal cancer?. Laryngoscope. 2003; 113: 2201–5.
• 21. el-Serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United Steates militery veterans. Gastroenterology. 1997; 113: 755-60.
• 22. Qadeer MA, Colabianchi N, Vaezi MF. Is GERD a risk factor for laryngeal cancer?. Laryngoscope. 2005; 115: 486–91.
• 23. Galli J, Cammarota G, Calò L, et al. The role of acid and alkaline reflux in laryngeal squamous cell carcinoma. Laryngoscope. 2002; 112: 1861–5.
• 24. Kim TH, Lee KJ, Yeo M, et al. Pepsin detection in the sputum/saliva for the diagnosis of gastroesophageal reflux disease in patients with clinically suspected atypical gastroesophageal reflux disease symptoms. Digestion. 2008; 77: 201-6.
• 25. Johnston N, Yan JC, Hoekzema CR, et al. Pepsin promotes proliferation in normal and transformed laryngopharyngeal epithelial cells. Laryngoscope. 2012; 122: 1317–25.
• 26. Shi SR, Key ME, Kalra KL. Antigen retrieval in formalin fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem. 1991; 39: 741–8
• 27. Tanca A, Pagnozzi D, Addis MF. Setting proteins free: progresses and achievements in proteomics of formalin-fixed, paraffin-embedded tissues. Proteomics Clin Appl. 2011; 6: 7–21.
• 28. Ostasiewicz P, Zielinska DF, Mann M, et al. Proteome, phosphoproteome, and N-glycoproteome are quantitatively preserved in formalin-fixed paraffin-embedded tissue and analyzable by high-resolution mass spectrometry. J Proteome Res. 2010; 9: 3688–700.
• 29. Balgley BM, Guo T, Zhao K, et al. Evaluation of archival time on shotgun proteomics of formalin-fixed and paraffin-embedded tissues. J Proteome Res. 2009; 8: 917-25.
• 30. Vaezi ME, Schroeder PL, Richter JE. Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal pH monitoring. Am J Gastroenterol. 1997; 92: 825-9.