Features of the expression of cyclin D1 and oncoprotein p27 in oropharyngeal squamous cell carcinomas with different proliferative potential

Authors

DOI:

https://doi.org/10.26641/1997-9665.2023.2.52-60

Keywords:

squamous cell carcinoma, oropharynx, cyclin D1, p16, HPV, p27.

Abstract

Background. Squamous cell carcinoma of the head and neck, including oral, pharyngeal, larynx, and sinonasal tract cancers, is the sixth most common cancer worldwide. The development of malignant tumors is associated with a series of changes in the activity of cell cycle regulators, which can be considered as positive and negative regulators. Positive regulators of the cell cycle can be considered cyclin A and cyclin D1, which contribute to the transition of the cell cycle from one phase to another; others, such as oncogene suppressors Rb, p16, p53, p21 and p27 are negative regulators that stop the cell cycle in the S phase. The aim of the study was to compare the expression levels of markers p27 and cyclin D1 in HPV-positive (p16+) and HPV-negative (p16-) squamous cell carcinomas of the oropharynx with different proliferative potential. Methods. In the work, the biopsy and surgical material of squamous cell carcinomas of 70 patients (22 women and 48 men) who were treated in the KP "Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikova Hospital of Dnipro in the period from 2019 to 2022. The age of the patients ranged from 41 to 80 years; the average age was 59.75±9.16 years. Primary monoclonal antibodies to p16 (RTU), p53 (RTU), Cyclin D1 (EP12, RTU), Ki-67 (sp6, RTU), p27 (sp1, RTU) and the UltraVision Quanto imaging system (LabVision) were used for immunohistochemical study. Results and conclusion. Cyclin D1 marker, analyzed in groups ≤10% and >10% according to clinical and morphological indicators showed a statistically significant difference in age (p<0.05) and histological type (keratinized/non-keratinized), (p<0.05) ; the analysis of cyclin D1 expression showed an inverse trend to the p16/HPV status, the largest number of 80.85% of cases of squamous cell carcinomas of the oropharyngeal area cyclin D1 with >10% were found among p16/HPV (-) observations; 91.30% of cases of squamous cell carcinoma of the oropharyngeal area with cyclin D1 ≤10% had p53 expression below the level of 25% (p<0.05); the largest number of cases of p27 expression with a high score (2+,3+) was noted among patients aged 40-49 years (p<0.05).

References

  1. Awawdeh MA, Sasikumar R, Aboalela AA, et al. Evaluation of Prognostic Significance of the Expression of p53, Cyclin D1, EGFR in Advanced Oral Squamous Cell Carcinoma after Chemoradiation – A Systematic Review. Appl. Sci. 2023;13(9):5292. https://doi.org/10.3390/app13095292.
  2. De C Ferreira C, Dufloth R, de Carvalho AC, et al. Correlation of p16 immunohistochemistry with clinical and epidemiological features in oropharyngeal squamous-cell carcinoma. PLoS One. 2021;16 (6):e0253418.
  3. Ramos-García P, González-Moles MÁ, González-Ruiz L, et al. Clinicopathological significance of tumor cyclin D1 expression in oral cancer. Archives of Oral Biology. 2019;99:177-182. https://doi.org/10.1016/j.archoralbio.2019.01.018.
  4. Vallonthaiel AG, Singh MK, Dinda AK, et al. Prognostic significance of cytoplasmic p27 in oral squamous cell carcinoma. J Oral Pathol Med. 2016;45(7):475-80. doi: 10.1111/jop.12392.
  5. Gao L, Gu W, Zheng J, et al. Clinicopathological and Prognostic Significance of p27 Expression in Oral Squamous Cell Carcinoma: A Meta-Analysis. The International Journal of Biological Markers. 2013;28(4):329-335. doi:10.5301/JBM.5000035.
  6. World Health Organіsatіon Classification of Head and Neck Tumours, 4th ed. A. K. El-Naggar, J. K. C. Chan, J. R. Grandis, T. Takata, P. J. Slootweg C. D. (Eds.). ІARC Press: Lyon, France, 2017. Vol. 9. P. 136-138.
  7. Shelton J, Purgina BM, Cipriani NA, et al. p16 immunohistochemistry in oropharyngeal squamous cell carcinoma: a comparison of antibody clones using patient outcomes and high-risk human papillomavirus RNA status. Modern Pathology. 2017;30:1194-1203. doi:10.1038/modpathol.2017.31.
  8. Updated WHO nomenclature of head and neck lesions and associated imaging findings. N. Oren, A. Vaysberg, D. T. Ginat. Insights into Imaging. 2019. Vol. 10. P. 72. https://doi.org/10.1186/s13244-019-0760-4.
  9. Adilbay D, Adilbayev G, Kidirbayeva G, et al. HPV infection and P16 expression in oral and oropharyngeal cancer in Kazakhstan. Infectious Agents and Cancer. 2018;13:2. DOI 10.1186/s13027-018-0175-8.
  10. Hashmi AA, Younus N, Naz S. p16 Immunohistochemical expression in head and neck squamous cell carcinoma: association with prognostic parameters. Cureus. Vol. 12 (6). P. e8601. doi:10.7759/cureus.8601.
  11. Benzerdjeb N, Tantot J, Blanchet C, et al. Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status. Histopathology. 2021;79(3):381-390. doi: 10.1111/his.14350
  12. Plath M, Broglie MA, Förbs D, et al. Prognostic significance of cell cycle-associated proteins p16, pRB, cyclin D1 and p53 in resected oropharyngeal carcinoma. J Otolaryngol Head Neck Surg. 2018;47(1):53. doi: 10.1186/s40463-018-0298-3.
  13. Hashmi AA, Hussain ZF, Hashmi SK, et al. Immunohistochemical over expression of p53 in head and neck squamous cell carcinoma: clinical and prognostic significance. BMC Res Notes. 2018;11(433):1-5. https://doi.org/10.1186/s13104-018-3547-7.
  14. Singla S, Singla G, Zaheer S, et al. Expression of p53, epidermal growth factor receptor, c-erbB2 in oral leukoplakias and oral squamous cell carcinomas. J Cancer Res Ther. 2018;14(2):388-393. doi: 10.4103/0973-1482.191027.
  15. Kumar B, Cordell KG, Lee JS, et al. EGFR, p16, HPV Titer, Bcl-xL and p53, Sex, and Smoking As Indicators of Response to Therapy and Survival in Oropharyngeal Cancer. J Clin Oncol. 2008 Jul 1; 26(19): 3128–3137. doi: 10.1200/JCO.2007.12.7662.
  16. Mohanapure NS, Khandeparkar SGS, Saragade PB, et al. Immunohistochemical study of epidermal growth factor receptor, human epidermal growth factor receptor 2/neu, p53, and Ki67 in oral squamous cell carcinoma. JOMFP. 2022;26(1):127-128. DOI: 10.4103/jomfp.jomfp_310_21.
  17. Vareniuk IM, Dzerzhynskyi ME. [Methods of cyto-histological diagnosis: study guide]. Kyiv. 2019. 256 p. Ukrainian.
  18. Nguyen T. Immunohistochemistry: A Technical Guide to Current Practices. Cambridge: Cambridge University Press. 2022. 272 p.
  19. Yadav P, Malik R, Balani S, et al. Expression of p16, Ki-67 and p53 markers in dysplastic and malignant lesions of the oral cavity and oropharynx. J Oral Maxillofac Pathol. 2019;23(2):224-230. doi: 10.4103/jomfp.JOMFP_299_18
  20. Queiroz AB, Focchi G, Dobo C et al. Expression of p27, p21WAF/Cip1, and p16INK4a in Normal Oral Epithelium, Oral Squamous Papilloma, and Oral Squamous Cell Carcinoma. Anticancer Research. 2010;30(7):2799-2803.
  21. Moharil RB, Khandekar S, Dive A, Bodhade A. Cyclin D1 in oral premalignant lesions and oral squamous cell carcinoma: An immunohistochemical study. Journal of Oral and Maxillofacial Pathology. 2020;24:397. doi: 10.4103/jomfp.JOMFP_164_20.
  22. Strahova OP, Androsov OI. [Statistical methods of processing the results of medical and biological research]. Lviv. 2021. 164 p. Ukrainian.
  23. Chaturvedi AK, Freedman ND, Abnet CC. The Evolving Epidemiology of Oral Cavity and Oropharyngeal Cancers. Cancer Res. 2022;82(16):2821-2823. https://doi.org/10.1158/0008-5472.CAN-22-2124.
  24. Robbins HA, Ferreiro-Iglesias A, Waterboer T, et al. Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium. Journal of Clinical Oncology. 2022;40(13):3613-3622. https://doi.org/10.1200/JCO.21.01785.
  25. Tsuchida K, Sugai T, Uesugi N, et al. Expression of cell cycle-related proteins in oropharyngeal squamous cell carcinoma based on human papilloma virus status. 2017;38(2):908-916. https://doi.org/10.3892/or.2017.5720.
  26. Gültekin SE, Sengüven B, Klussmann JP, Dienes HP. p16INK 4a and Ki-67 expression in human papilloma virus-related head and neck mucosal lesions. Invest Clin. 2015;56(1):47-59.
  27. Anand C, Pallavi K, Pravin G, et al. Expression of cyclin D1 in oral squamous cell carcinoma and its correlation with histological differentiation An immunohistochemical study. Journal of Indian Academy of Oral Medicine and Radiology. 2016;28(2):140-144. DOI: 10.4103/0972-1363.195099.

Published

2025-04-19

How to Cite

Rakhmanov , V., & Shponka , I. (2025). Features of the expression of cyclin D1 and oncoprotein p27 in oropharyngeal squamous cell carcinomas with different proliferative potential. Морфологія / Morphologia / Morfologìâ, 17(2), 52–60. https://doi.org/10.26641/1997-9665.2023.2.52-60

Issue

Section

Статті