Immunohistochemical Eexpression of Endothelin A Receptor in Dysplastic Oral Mucosa

Document Type: Short Communication


1 Babol University of Medical Sciences, Babol, Iran

2 Associate Professor, Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Birjand University of Medical Sciences, Birjand, Iran

3 Assistant Professor, Pathology Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Institute of Health, Babol University of Medical Sciences, Babol, Iran


Background: Recent researches have provided evidences of the importance of endothelin axis in carcinogenesis. According to our knowledge, no data exists about endothelin A receptor (ETA) expression in dysplastic oral mucosa (DOM). Therefore, the aim of the present study was to evaluate immunohistochemical expression of ETA in DOM.
Methods:In this cross-sectional study, paraffin-embedded tissue blocks of 20 cases of DOM and 20 cases of normal oral mucosa (NOM) were studied. Three-micron sections were prepared from tissue blocks and stained with ETA antibody using immunohistochemistry. Percentage of stained cells and staining intensity were compared between DOM and NOM groups and also between different grades of DOM using Mann-Whitney, Chi-Square and Kruskal-Wallis statistical tests.
Results:In DOM group, 11 cases were stained positive for ETA and in NOM group 17 cases were not stained. Comparison of percentage of stained cells and staining intensity for ETA revealed significant difference between DOM and NOM groups (P=0.01 and 0.02, respectively). There were significant differences among different grades of DOM with respect to the percentage of stained cells (P=0.001) and staining intensity (P=0.02), so that higher grades showed greater expression for ETA.
Conclusion:Our results supported ETA receptor role in the initiation of carcinogenesis process in oral cavity.


  1. Afsharnejat A, Sharbatdaran M, Gholinia H, Abbaszadeh H. Comparative evaluation of complement factor I in dysplastic and normal oral mucosa using immunohistochemistry. Journal of Research in Dental Sciences 2016; 13(3):117-21. [In Persian].
  2. Ranjisaraay N, Sharbatdaran M, Gholinia H, Abbaszadeh H. Assessment the role of complement factor I in oral squamous cell carcinoma. Journal of Research in Dental Sciences 2017; 13(4):196-200. [In Persian].
  3. Ishimoto S, Wada K, Tanaka N, Yamanishi T, Ishihama K, Aikawa T, et al. Role of endothelin receptor signalling in squamous cell carcinoma. Int J Oncol 2012; 40(4):1011-9.
  4. Bagnato A, Natali PG. Endothelin receptors as novel targets in tumor therapy. J Transl Med 2004; 2(1):16.
  5. Alaizari NA, Abdelbary SN, Amin NR. Immunohistochemical expression of endothelin protein in oral squamous cell carcinoma. Indian J Pathol Microbiol 2013; 56(2):151-4.
  6. Hoffmann RR, Yurgel LS, Campos MM. Endothelins and their receptors as biological markers for oral cancer. Oral Oncol 2010; 46(9):644-7.
  7. Neville B, Daam DD, Allen C, Chi A. Oral and Maxillofacial Pathology. 4th ed. Missouri: Saunders; 2015. p. 410-21.
  8. Wülfing P, Tio J, Kersting C, Sonntag B, Buerger H, Wülfing C, et al. Expression of endothelin-A-receptor predicts unfavourable response to neoadjuvant chemotherapy in locally advanced breast cancer. Br J Cancer 2004; 91(3):434-40.
  9. Salem SA, Gamal Aly D, Salah Youssef N, Moneim El-Shaer MA. Immunohistochemical assessment of endothelin-1 axis in psoriasis, basal cell carcinoma and squamous cell carcinoma. G Ital Dermatol Venereol 2015; 150(3):283-91.
  10. Ishibashi Y, Hanyu N, Nakada K, Suzuki Y, Yamamoto T, Takahashi T, et al. Endothelin protein expression as a significant prognostic factor in oesophageal squamous cell carcinoma. Eur J Cancer 2003; 39(10):1409-15.
  11. Awano S, Dawson LA, Hunter AR, Turner AJ, Usmani BA. Endothelin system in oral squamous carcinoma cells: specific siRNA targeting of ECE‐1 blocks cell proliferation. Int J Cancer 2006; 118(7):1645-52.
  12. Pickering V, Jordan RC, Schmidt BL. Elevated salivary endothelin levels in oral cancer patients-a pilot study. Oral Oncol 2007; 43(1):37-41.
  13. Hinsley EE, Hunt S, Hunter KD, Whawell SA, Lambert DW. Endothelin‐1 stimulates motility of head and neck squamous carcinoma cells by promoting stromal–epithelial interactions. Int J cancer 2012; 130(1):40-7.
  14. Cong N, Li Z, Shao W, Li J, Yu S. Activation of ETA receptor by endothelin-1 induces hepatocellular carcinoma cell migration and invasion via ERK1/2 and AKT signaling pathways. J Membr Biol 2016; 249(1-2):119-28.