Dentist № 1 (48) – 2023, pp. 50-58                                                                                                             SCIENTIFIC PUBLICATION


Immunohistochemical features of Ki-67, PCNA and p53 expression in leukoplakia and squamous cell carcinoma of oral mucosa


N.A. Karpuka, S.P. Rubnikovichb, M.N. Medvedeva, V.A. Klopovaa

aMD, PhD, Associate Professor, Vitebsk State Medical University, Vitebsk, Belarus
b MD, PhD, DMSci, Professor, Belarusian State Medical University, Minsk, Belarus

https://doi.org/10.32993/dentist.2023.1(48).11

ABSTRACT
The aim of the study. To study the features of the processes of proliferation and apoptosis in terms of the expression of proteins Ki-67, PCNA and p53 at various degrees of epithelial dysplasia in leukoplakia and squamous cell carcinoma of the oral mucosa.
Objects and methods. An immunohistochemical study of the expression of proteins Ki-67, PCNA and p53 in leukoplakia and squamous cell carcinoma of the oral mucosa (OМ) was carried out.
Results and discussion. With an increase in the degree of dysplastic changes in LOМ, an increase in the number of cells with impaired apoptosis is observed, reaching a maximum in grade III dysplasia; the most pronounced expression of p53 was in squamous cell carcinoma (p<0.05). In the unchanged epithelium of OМ, Ki-67 expression was detected only in the basal layer, while in dysplasia it was detected in the parabasal and spiny layers, and in squamous cell carcinoma – in all areas of the tumor. In LOМ with grade III dysplasia, immunopositive cell nuclei were detected in all layers of the epithelial layer. As the degree of dysplasia increased, the Ki-67 proliferation index increased in the parabasal and overlying layers and decreased in the basal layer. Data on the distribution of Ki-67 and PCNA-immunoreactive cells showed an increase in mitotic activity from the basal to the overlying layers of the epithelium as the severity of dysplastic changes increases.
Conclusion. Mitotic activity (according to Ki-67 and PCNA expression data) in squamous cell carcinoma is higher than in grade III dysplasia (p < 0.05), which makes it possible to use these markers, as well as p53, in the complex differential diagnosis of squamous cell carcinoma and LOМ with grade III dysplasia.

Keywords: immunohistochemistry, leukoplakia, mucosal cancer, Ki-67, PCNA, p53 expression

References 

  1. Karpuk К.A., Rubnikovich S.P., Boginskij O.Ju. Vozmozhnosti citologicheskoj diagnostiki v dispanserizacii pacientov s predopuholevymi zabolevanijami slizistoj obolochki rta s uchetom ih rasprostranennosti v Vitebskoj oblasti s 2014 po 2019 gg. [Possibilities of cytological diagnostics in clinical examination of patients with precancerous diseases of the oral mucosa, taking into account their prevalence in the Vitebsk region from 2014 to 2019]. VGMU. – Bulletin of VSMU. 2020, vol. 19, no. 2, pp. 78-88.
  2. Karpuk I.Ju., Novikov D.K. Vyjavlenie allergii i giperchuvstvitel’nosti k soljam metallov putem opredelenija urovnja ionov kalija v rotovoj zhidkosti [Detection of allergies and hypersensitivity to metal salts by determining the level of potassium ions in the oral fluid]. Immunopatologija, allergologija, infektologija. – Immunopathology, allergology, infectology. 2016, no. 3, pp. 21-30.
  3. Karpuk I.Ju. Immunopatologija u pacientov s ortopedicheskimi konstrukcijami v polosti rta [Immunopathology in patients with orthopedic constructions in the oral cavity]. Vestn. VGMU. – Bulletin of VSMU. 2014, vol. 13, no. 4, pp. 29-35.
  4. Karpuk I.Ju., Fadeev V.I. Vydelenie ionov metallov iz stomatologicheskih splavov i ih vlijanie na metabolicheskuju i killingovuju aktivnost’ lejkocitov [Isolation of metal ions from dental alloys and their effect on the metabolic and killing activity of leukocytes]. Immunopatologija, allergologija, infektologija. – Immunopathology, allergology, infectology. 2017, no. 3, pp. 6-21.
  5. Karpuk I.Ju. Znachenie matriksnyh metalloproteinaz-8 i -9 v razvitii allergopatologii slizistoj obolochki polosti rta, vyzvannoj neperenosimost’ju zuboproteznyh materialov [Significance of matrix metalloproteinases-8 and -9 in the development of allergopathology of the oral mucosa caused by intolerance to denture materials]. Vestn. VGMU. – Bulletin of VSMU. 2015, vol. 14, no. 2, pp. 89-96.
  6. Barnes L. [et al.] Pathology and Genetics of Head and Neck Tumours. IARC Press, 2005. 430 p.
  7. Barnes L. [et al.] Pathology and Genetics of Head and Neck Tumours. World Health Organization Classification of Tumours. 3-th ed. Lyon: IARC Press, 2005. pp. 177-179.
  8. Chiang C.P. [et al.] Expression of proliferating cell nuclear antigen (PCNA) in oral submucous fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan. Oral Oncol., 2000 Jul, vol. 36, no. 4, pp. 353-359, doi: 10.1016/s1368-8375(00)00014-2.
  9. Imaizumi T. [et al.] Detection of Endogenous DNA Double-strand Breaks in Oral Squamous Epithelial Lesions by P53-binding Protein 1. Anticancer Res., 2021 Oct, vol. 41, no. 10, pp. 4771-4779, doi: 10.21873/anticanres.15292.
  10. Iocca O. [et al.] Potentially malignant disorders of the oral cavity and oral dysplasia: A systematic review and meta-analysis of malignant transformation rate by subtype. Head Neck., 2020 Mar, vol. 42, no. 3, pp. 539-555, doi: 10.1002/hed.26006.
  11. Matsuhira A. [et al.] Cytokeratin 13, Cytokeratin 17, Ki-67 and p53 Expression in Upper Layers of Epithelial Dysplasia Surrounding Tongue Squamous Cell Carcinoma. Bull Tokyo Dent Coll., 2015, vol. 56, no. 4, pp. 223-231, doi: 10.2209/tdcpublication.56.223. PMID: 26657521.
  12. Sanketh D.S. [et al.] Expression of Ki-67, p53, α-SMA and COX-2 in lichen planus and related lesions: A pilot study. J Oral Biol Craniofac Res., 2019 Apr-Jun, vol. 9, no. 2, pp. 230-235, doi: 10.1016/j.jobcr.2018.02.003.
  13. Sousa F.A. [et al.] Immunohistochemical expression of PCNA, p53, bax and bcl-2 in oral lichen planus and epithelial dysplasia. J Oral Sci., 2009 Mar, vol. 51, no. 1, pp. 117-121, doi: 10.2334/josnusd.51.117.
  14. Speight P.M., Khurram S.A., Kujan O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg. Oral Med. Oral Pathol. Oral Radiol., 2018 Jun, vol. 125, no. 6, pp. 612-627, doi: 10.1016/j.oooo.2017.12.011.
  15. Suwasini S. [et al.] Expression of P53 Protein and Ki-67 Antigen in Oral Leukoplakia with Different Histopathological Grades of Epithelial Dysplasia. J Int Soc Prev Community Dent., 2018 Nov-Dec, vol. 8, no. 6, pp. 513-522, doi: 10.4103/jispcd.JISPCD_241_18.
  16. Uehara M. [et al.] Predictive factor for photodynamic therapy effects on oral squamous cell carcinoma and oral epithelial dysplasia. Arch Oral Biol., 2011 Nov, vol. 56, no. 11, pp. 1366-1372, doi: 10.1016/j.archoralbio.2011.04.012.
  17. Ueki N. [et al.] Detection of Endogenous DNA Double-strand Breaks in Oral Squamous Epithelial Lesions by P53-binding Protein 1. Anticancer Res., 2021 Oct, vol. 41, no. 10, pp. 4771-4779, doi: 10.21873/anticanres.15292.
  18. Vered M., Allon I., Dayan D. Maspin, p53, p63, and Ki-67 in epithelial lesions of the tongue: from hyperplasia through dysplasia to carcinoma. J Oral Pathol Med., 2009 Mar, vol. 38, no. 3, pp. 314-320, doi: 10.1111/j.1600-0714.2008.00698.x.
  19. Warnakulasuriya, S., Johnso, N. W., Van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med., 2007 Nov, vol. 36, no. 10, pp. 575-580, doi: 10.1111/j.1600-0714.2007.00582.x.
  20. Woo, S. B. Oral Epithelial Dysplasia and Premalignancy. Head Neck Pathol., 2019 Sep., vol. 13, no. 3, pp. 423-439, doi: 10.1007/s12105-019-01020-6.

Correspondence to:  Е-mail: ms.karpuk@mail.ru