Year 2014 Vol. 22 No 6

OTORHINOLARYNGOLOGY

A.L. MALETS 1, S.N. RJABCEVA2, J.G. ROMANOVA1, V.P. SHORATS1

CYCLOOXYGENASE-2 ROLE IN PATHOGENESIS OF THE LARYNGEAL PAPILLOMATOSIS IN ADULTS

EE "Belarusian Medical Academy of Post-Graduate Education"1,
EE “Belarusian State Medical University” 2,
The Republic of Belarus

Objectives. On the basis of the immunohistochemical analysis to study the expression of cyclooxygenase-2 (COX-2) marker depending on the degree of dysplasia in the laryngeal papilloma tissue in adults.
Methods. The papilloma tissue fragments (62) obtained during the surgical treatment of the larynx with the tumor removal in adult patients with respiratory papillomatosis have been served as a research material. The evaluation of the dysplasia degree in the papilloma tissue was performed. The immunohistochemical assessment of expression of COX-2 monoclonal antibody in cells of the laryngeal papillomas has been conducted.
Results. The first studied group consisted of patients with laryngeal papilloma without epithelial dysplasia (7/11,3%), the second – with dysplasia of the first (mild) degree (12/19,4%), the third – with a second-degree dysplasia (moderate) (28/45,2%), the fourth – with severe dysplasia (9/14,5%), the fifth – with laryngeal cancer against a background of papillomatosis (6/9,7%). The reliable difference of the studied groups according to the weak expression intensity in the epithelial cells of laryngeal papillomas with the inverse correlation interrelation has been established. The moderate growth of expression COX-2 in the cells with dysplasia was revealed in comparison with papillomas without dysplasia. The highest figure of intensity of moderate expression and substantially equal value found in the groups of the first and second degree of epithelial dysplasia papillomas have been recorded. Reliable difference between the studied groups in severe expression intensity in cells of the laryngeal papillomas with the direct correlations has been established. The laryngeal cancer cells had the highest intensity value of severe COX-2 expression.
Conclusion. In the cells of laryngeal papillomas in adults the increase of the intensity of immunohistochemical COX-2 markers with increasing degree of dysplasia testifing the activity of this enzyme has been observed. COX-2 is considered to be an important factor in the pathogenesis of laryngeal papillomatosis in adults, and it plays one of the key roles in malignant transformation and progression of neoplasms.

Keywords: papilloma, larynx, cyclooxygenase-2, dysplasia
p. 727-734 of the original issue
References
  1. Blumin JH, Handler EB, Simpson CB, Osipov V, Merati AL. Dysplasia in adults with recurrent respiratory papillomatosis: incidence and risk factors. Ann Otol Rhinol Laryngol. 2009 Jul;118(7):481–85.
  2. Hall JE, Chen K, Yoo MJ, Fletcher KC, Ossoff RH, Garrett CG.Natural progression of dysplasia in adult recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 2011 Feb;144(2):252–56.
  3. Sajan JA, Kerschner JE, Merati AL, Osipov V, Szabo S, Blumin JH.Prevalence of dysplasia in juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg. 2010 Jan;136(1):7–11.
  4. Dannenberg AJ, Subbaramaiah K.Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell. 2003 Dec;4(6):431–36.
  5. Thun MJ, Henley SJ, Patrono C.Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst. 2002 Feb 20;94(4):252–66.
  6. Moldan M, Bostrom B, Meixia Liu, Tibesar R, Sidman D, Lander T. EGFR inhibitor therapy for laryngeal papillomatosis. Otolaryngol Head Neck Surg. 2012;147 (2S):230.
  7. Limsukon A, Susanto I, Hoo GW, Dubinett SM, Batra RK.Regression of recurrent respiratory papillomatosis with celecoxib and erlotinib combination therapy. Chest. 2009 Sep;136(3):924–26.
  8. Jaeckel EC, Raja S, Tan J, Das SK, Dey SK, Girod DA, Tsue TT, Sanford TR.Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2001 Oct;127(10):1253–59.
  9. Wu R, Abramson AL, Shikowitz MJ, Dannenberg AJ, Steinberg BM.Epidermal growth factor-induced cyclooxygenase-2 expression is mediated through phosphatidylinositol-3 kinase, not mitogen-activated protein/extracellular signal-regulated kinase kinase, in recurrent respiratory papillomas. Clin Cancer Res. 2005 Sep 1;11(17):6155–61.
  10. Lucs AV, Wu R, Mullooly V, Abramson AL, Steinberg BM. Constitutive overexpression of the oncogene Rac1 in the airway of recurrent respiratory papillomatosis patients is a targetable host-susceptibility factor. Mol Med. 2012 Mar 30;18:244–49.
  11. Yoo HJ, Sepkovic DW, Bradlow HL, Yu GP, Sirilian HV, Schantz SP.Estrogen metabolism as a risk factor for head and neck cancer. Otolaryngol Head Neck Surg. 2001 Mar;124(3):241–47.
  12. Salhab M, Singh-Ranger G, Mokbel R, Jouhra F, Jiang WG, Mokbel K.Cyclooxygenase-2 mRNA expression correlates with aromatase expression in human breast cancer. J Surg Oncol. 2007 Oct 1;96(5):424–28
  13. Chan G, Boyle JO, Yang EK, Zhang F, Sacks PG, Shah JP, Edelstein D, Soslow RA, Koki AT, Woerner BM, Masferrer JL, Dannenberg AJ. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res. 1999 Mar 1;59(5):991–94.
  14. Grinevich IuA, Baraboi VA. Novoobrazovatel'nyi protsess i stressovaia patologiia [Neroplasms and stress pathology]. Kiev, Ukraina: Logos, 2010. 155 p.
  15. Zhang P, Steinberg BM.Overexpression of PTEN/MMAC1 and decreased activation of Akt in human papillomavirus-infected laryngeal papillomas. Cancer Res. 2000 Mar 1;60(5):1457–62.
  16. Wu R, Coniglio SJ, Chan A, Symons MH, Steinberg BM. Up-regulation of Ras-1 by epidermal growth factor mediates COX-2 expression in recurrent respiratory papillomatosis. Mol Med. 2007 Mar-Apr; 13(3-4):143–50.
Address for correspondence:
220013, Respublika Belarus,
g. Minsk, ul. P. Brovki, d. 3, korp. 3,
GUO «Belorusskaya meditsinskaya akademiya
poslediplomnogo obrazovaniya»,
kafedra otorinolaringologii,
tel. mob.: 375 29 1020548,
e-mail: malets-al@yandex.ru,
Malets Elena Leonidovna
Information about the authors:
Malets E.L. A post-graduate student of the otorhinolaryngology chair of EE “Belarusian Medical Academy of Post-graduate Education”.
Rjabceva S.N. PhD, an assistant of the pathologic anatomy chair of EE “Belarusian State Medical University”.
Romanova J.G. PhD, associate professor of the otorhinolaryngology chair of EE “Belarusian Medical Academy of Post-graduate Education”.
Shorats O.P. An junior researcher of the research laboratory of EE “Belarusian Medical Academy of Post-graduate Education”.
Contacts | ©Vitebsk State Medical University, 2007-2023