EXPRESSION CHARACTERISTICS OF MARKERS OF PROLIFERATIVE ACTIVITY, APOPTOSIS AND CELL DIFFERENTIATION IN PATIENTS WITH PREMALIGNANT LESIONS AND CANCER OF THE LARYNX
Abstract
The purpose of the study was to determine the informative value of р53, CD 138 and Кi 67 markers in mucosal stratified squamous epithelium of patients with precancerous laryngeal lesions and laryngeal cancer. Material and methods. Expression of the above markers was analyzed in 80 patients with chronic laryngeal diseases and in 37 patients with laryngeal cancer. Results. The level of proliferative activity was shown to be directly proportional to more severe dysplastic and neoplastic lesions of the laryngeal mucosa, thus indicating the increased proliferative activity in precancerous lesions and their subsequent malignant transformation. Our data clearly show that suppression of apoptosis is one of the mechanisms of malignant epithelial transformation of epithelial cells. In difficult cases, a sharp increase in the levels of p53 and KI 67 in patients with grade III dysplasia can be considered as an additional criterion for evaluation of risk of malignant transformation. Based on the results obtained, CD138, a cell differentiation marker, is recommended to be considered as an additional criterion for selecting patients with grade II dysplasia into the group being at high risk for laryngeal cancer development. Conclusion. Persistently increased Ki67 expression level serves as an additional criterion for inclusion of patients with precancerous lesions to the group at increased risk of cancer. Alterations in the expression levels of р53 in patients with grade III laryngeal dysplasia are the signs of possible progression of premalignant lesions.
About the Authors
О. V. CheremisinaRussian Federation
Cheremisina Olga Vladimirovna, MD, DSc, Head of Endoscopy Department.
E-mail: СheremisinaOV@oncology.tomsk.ru. SPIN-code: 9579-2691.
O. V. Pankova
Russian Federation
Pankova Olga Vladimirovna, PhD, Senior Researcher, Department of Pathological Anatomy and Cytology.
E-mail: pankovaov1903@yandex.ru. SPIN-code: 3355-7118.
К. Yu. Menshikov
Russian Federation
Menshikov Kirill Yurievich, physician, Endoscopy Department.
E-mail: kiri_78@mail.ru
E. L. Choinzonov
Russian Federation
Choinzonov Evgeny Lhamatsirenovich, MD, DSc, Professor, Academician of RAS, Director of the Tomsk Cancer Research Institute.
E-mail: nii@oncology.tomsk.ru. SPIN-code: 2240-8730
References
1. Gorban' N.A., Kudaĭbergenova A.G., Pankratov V.A. Prognostic value of markers for proliferative activity and apoptotic regulation in laryngeal squamous cell carcinoma // Arhiv patologii. Vol. 75 (1). P. 3–9. [in Russian]
2. Kaprin A.D., Starinskij V.V., Petrova G.V. Cancer incidence in Russia in 2013 (morbidity and mortality). M., 2015. P. 250. [in Russian]
3. Kovalenko S.N., Lapchenko A.S., Muratov D.L. Problems of diagnosis of chronic hyperplastic laryngitis // Vestnik otorinolaringologii. 2006. № 4. P. 27–30. [in Russian]
4. Kulagin R.N. Is p53 a prognostic factor in patients with laryngeal carcinoma? // Rossijskaja otorinolaringologija. 2012. № 6 (61). P. 92–95. [in Russian]
5. Muhamedov M.R., Cheremisina O.V., Choynzonov E.L., Kulbakin D.E., Balatskaya L.N., Vasiliev N.V., Gunther V.E. The modern view on complex approach when diagnosing, treating and aftercaring in larynx cancer patients // Rossijskaja otorinolaringologija. 2012. № 3. P. 78–84. [in Russian]
6. Mukhamedov M.R., Choinzonov E.L., Gunter V.E., Cheremisina O.V., Lukyanov V.D., Myadzel A.A., Shinkarev S.A., Korenev A.A., Vasiliev N.V., Tsvetayev V.A., Kulbakin D.E. Titanium nikcekide-based bioadapted implants in surgical rehabilitation of patients with laryngeal cancer (results of a ten-year cooperative study) // Vestnik RONC im. N. N. Blohina RAMN. 2010. Vol. 21 (1). P. 65–70. [in Russian]
7. Paches A.I. Tumors of the head and neck. M., 2013. 478 p. [in Russian]
8. Poddubnyj B.K., Belousova N.V., Ungiadze G.V. Diagnostic and therapeutic endoscopy of the upper respiratory tract. M., 2006. 256 p. [in Russian]
9. Sokolov V.V., Telegina L.V., Gladyshev A.A., Frank G.A., Zavalishina L.E., Belous T.A. Modern methods of diagnostics of obligate premalignancy and early laryngeal cancer // Opuholi golovy i shei. 2013. № 3. P. 44–48. [in Russian]
10. Cheremisina O.V., Choinzonov E.L. Potentials of endoscopic diagnosis of precancer diseases and cancer of the larynx // Sibirskij onkologicheskij zhurnal. 2007. № 3. P. 5–9. [in Russian]
11. Choinzonov E.L. Cancer of the upper respiratory and digestive tract (epidemiological and immunovirological aspects, assessment of treatment effectiveness ): Author’s thesis. Tomsk, 1995. 46 p. [in Russian]
12. Ashraf M.J., Maghbul M., Azarpira N., Khademi B. Expression of Ki67 and P53 in primary squamous cell carcinoma of the larynx // Indian. J. Pathol. Microbiol. 2010. Vol. 53 (4). P. 661–665. doi: 10.4103/03774929.72019.
13. Nunes R.B., Behlau M., Nunes M.B., Paulino J.G. Clinical diagnosis and histological analysis of vocal nodules and polyps // Braz. J. Otorhinolaryngol. 2013. Vol. 79 (4). P. 434–440. doi: 10.5935/1808-8694.2013007.
14. Cosway B., Paleri V. Laryngeal dysplasia: an evidence-based flowchart to guide management and follow up // J. Laryngol. Otol. 2015. Vol. 129 (6). P. 598–599. doi: 10.1017/S0022215115000833.
15. Hu Y., Liu H. Histopathological variability and the prognosis of laryngeal premalignant lesions // Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014. Vol. 49 (12). P. 979–985.
16. Hussein M.R. Alterations of p53 and Bcl-2 protein expression in the laryngeal intraepithelial neoplasia // Cancer Biol. Ther. 2005. Vol. 4 (2). P. 213–217.
17. Ioachim E., Peschos D., Goussia A., Mittari E., Charalabopoulos K., Michael M., Salmas M., Vougiouklakis T., Assimakopoulos D., Agnantis N.J. Expression patterns of cyclins D1, E in laryngeal epithelial lesions: correlation with other cell cycle regulators (p53, pRb, Ki-67 and PCNA) and clinicopathological features // J. Exp. Clin. Cancer Res. 2004. Vol. 23 (2). P. 277–283.
18. Micozkadioğlu D., Unal M., Pata Y.S., Baştürk M., Cinel L. Prognostic value of expression of p53, proliferating cell nuclear antigen, and c-erbB-2 in laryngeal carcinoma // Med. Sci. Monit. 2008. Vol. 14 (6). P. 299–304.
19. Pastuszewski W., Dziegiel P., Krecicki T., Podhorska-Okolow M., Ciesielska U., Gorzynska E., Zabel M. Prognostic significance of metallothionein, p53 protein and Ki-67 antigen expression in laryngeal cancer // Anticancer Res. 2007. Vol. 27 (1A). P. 335–342.
20. Rodrigo J.P., García-Pedrero J.M., Suárez C., Takes R.P., Thompson L.D., Slootweg P.J., Woolgar J.A., Westra W.H., Brakenhoff R.H., Rinaldo A., Devaney K.O., Williams M.D., Gnepp D.R., Ferlito A. Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review // Eur. Arch. Otorhinolaryngol. 2012. Vol. 269 (4). P. 1073–1083. doi: 10.1007/s00405-011-1831-4.
21. Şimşek H., Han Ü., Önal B., Şimişek G. The expression of EGFR, cerbB2, p16, and p53 and their relationship with conventional parameters in squamous cell carcinoma of the larynx // Turk. J. Med. Sci. 2014. Vol. 44 (3). P. 411–416.
Review
For citations:
Cheremisina О.V., Pankova O.V., Menshikov К.Yu., Choinzonov E.L. EXPRESSION CHARACTERISTICS OF MARKERS OF PROLIFERATIVE ACTIVITY, APOPTOSIS AND CELL DIFFERENTIATION IN PATIENTS WITH PREMALIGNANT LESIONS AND CANCER OF THE LARYNX. Siberian journal of oncology. 2015;1(5):74-79. (In Russ.)