Immunohistochemical characteristic of expression levels of Kі-67, p16INK4a, HPV16 in cervical intraepithelial neoplasia and cervical cancer
DOI:
https://doi.org/10.14739/2310-1237.2017.2.109298Keywords:
cervix uteri, uterine cervical neoplasms, human papilloma virus, Ki-67 antigenAbstract
Squamous cervical cancer (SCC) is a common tumor in women, which is preceded by the series of pathological processes, among which the key role is played by cervical intraepithelial neoplasia (CIN).
Aim. To study the characteristics of immunohistochemical (IHC) expression of Ki-67, p16INK4a, HPV16 in squamous cervical epithelium (SCE) with dysplastic changes of varying degree (CIN I–III) and also in the tumor cells of SCC.
Materials and methods. Pathohistological and IHC studies of uterine cervix biopsies from 53 patients (the age ranged from 18 to 45 years) were performed.
Results. It was found that SCE with CIN I is characterized by the low Ki-67 expression level (Me = 17.87 % (13.76, 22.44)) and the extremely low p16INK4a expression level (Me = 0.00 CUOD (0.00; 29.64)). The proportion of HPV16-positive patients with CIN I is 27.27 %. CIN II is characterized by the average proliferation level in SCE (Me = 44.96 % (34.91, 55.41)) and the moderate p16INK4a expression level (Me = 75.71 CUOD (51.24, 82, 41)). The proportion of HPV16-positive patients with CIN II is 71.43 %. CIN III is characterized by the high proliferation level (Me = 74.62 % (68.50, 84.67)) and by the high p16INK4a expression level of in SCE (Me = 117.47 CUOD (95.38, 123, 93)); the proportion of HPV16-positive patients with CIN III is 77.78%. In all the patients with SСС, nuclear and cytoplasmic expression of HPV16 was detected in the tumor cells. High expression levels of Ki-67 and p16INK4a were detected in the tumor cells. There are direct correlations between the expression levels of Ki-67, p16INK4a, HPV16 and CIN degree.
Conclusions. These data indicate that the expression levels of Ki-67, p16INK4a and HPV16 increase with the increasing of CIN grade. The absence of statistically significant differences between the expression levels of Ki-67, p16INK4a and HPV16 in CIN III and the same levels in the tumor cells of SCC indicates that these markers cannot be used for differential diagnosis between CIN III and SCC.
References
Fedorenko, Z. P., Hulak, L. O., Mykhailovych, Yu. I., et al. (2015) Zakhvoriuvanist ta smertnist vid zloiakisnykh novoutvoren. Stan onkolohichnoi dopomohy naselenniu [Incidence and mortality from malignant neoplasms. The state of oncological care to the population]. Rak v Ukraini, 2013–2014: biuleten natsionalnoho kantser-reiestru Ukrainy, 16, 1–6. [in Ukrainian].
Tumanskyi, V. O., Yevsieiev, A. V., Kovalenko, I. S., & Zubko, M. D. (patentee) (2015) Patent 99314 Ukraina, MPK 2015.01 G01N 21/00 G06K 9/00 Sposib fototsyfrovoi morfometrii imunohistokhimichnykh preparativ [Patent of Ukraine 99314, IPC 2015.01 G01N 21/00 G06K 9/00 The technique of digital morphometry of immunohistochemical slides]. Biuleten, 10 [in Ukrainian].
Burtushkina, N. K, Kupert, A. F., & Kokunova, E. G. (2011) Structura neopukholevykh zabolevanij shejki matki [The structure of nonneoplastic diseases of cervix uteri]. Sibirskij medicinskij zhurnal, 102(3), 121–123 [in Russian].
Dolzhikov, A. A. (2013) Immunomorfologicheskoe issledovanie metabolicheskikh i proliferativnykh markerov pri ploskokletochnom rake shejkimatki [Immunomorphologycal investigation of metabolic and proliferation markers in squamous cell carcinoma of the uterine cervix]. Vestnik novykh medicinskikh tekhnologij, 1, 233. [in Russian].
Zakharseva, L. M., & Pecur, E. A (2013) Chastota e´kspressii belka p16INK4a i nalichie virusov papilommy cheloveka pri displasii shejki matki [Frequency of protein p16INK4a expression and availability for human papilloma virus in cervical dysplasia]. Oncologiya, 15(1), 9–13. [in Russian].
Gupta, K., Alam, K., Maheshwari, V., Khan, R., & Sharma, R. (2013) Apoptotic Index and Mib-1 Antibody Expression in Premalignant and Malignant Lesions of Uterine Cervix. Gynecology & Obstetrics, 3, 117–22. doi: 10.4172/2161-0932.1000173.
Albero, G., Barrionuevo-Rosas, L., & Bosch, F. X. (2016) Human Papillomavirus and Related Diseases. Report.
Bosch, F. X, Broker, T. R., Forman, D., Moscicki, A. B., Gillison, M. L., Doorbar, J., et al. (2013) Comprehensive Control of Human Papillomavirus Infections and Related Diseases. Vaccine, 31, 1–31. doi: 10.1016/j.vaccine.2013.10.003.
Dabbs, D. J. (2010) Diagnostic Immunohistochemistry. New York: Ch. Livingstone.
Kitchener, H. C., Denton, K., Soldan, K., & Crosbie, E. J. (2013) Developing role of HPV in cervical cancer prevention. BMJ, 347, 4781–4789. doi: https://doi.org/10.1136/bmj.f4781.
Mimica, M., Tomić, S., Kardum, G., Hofman, I. D., Kaliterna, V., & Pejković, L. (2010) Ki-67 Quantitative Evaluation as a Marker of Cervical Intraepithelial Neoplasia and Human Papillomavirus Infection. International Journal of Gynecological Cancer, 20(1), 116–119 doi: 10.1111/IGC.0b013e3181bc8da7.
Godoy, A., Bazzo, K., & Pasqualotto, F. (2014) HPV pathogenesis and biomarkers of viral progression and cervical cancer: A literature review. World Journal of Biology and Biological Sciences, 2(1), 26–33.
Sigurdsson, K., Taddeo, F. J., Benediktsdottir, K. R., Olafsdottir, K., Sigvaldason, H., Oddsson, K., & Rafnar, T. (2007) HPV genotypes in CIN 2-3 lesions and cervical cancer: A population-based study. International Journal of Cancer, 121, 2682–2687. doi:10.1002/ijc.23034.
Zhong, P., Li, J., Gu, Y., Liu, Y., Wang, A., Sun, Y., & Lu, L. (2015). P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1. Int. J. of Clin.and Experim. Path., 8(3), 2979–2986.
Godoy, A. E. G., Mandelli, J., Oliveira, F. H., Calegari, S., Moura, L. B., & Serafini, E. P. (2008) p16INK4 expression in precursor lesions of squamous cell cervical cancer related to the presence of HPV-DNA. Braz. J. Med. and Biol. R., 41, 583–8.
Donà, M. G., Vocaturo, A., Giuliani, M., Ronchetti, L., Rollo, F., Pescarmona, E., et al. (2012) p16/Ki-67 dual staining in cervico-vaginal cytology: correlation with histology, Human Papillomavirus detection and genotyping in women undergoing colposcopy. Gynecologic Oncology, 126(2), 198–202. doi: 10.1016/j.ygyno.2012.05.004.
Petry, K. U., Schmidt, D., Scherbring, S., Luyten, A., Reinecke-Lüthge, A., Bergeron, C., et al. (2011) Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology. Gynecologic Oncology, 121, 505–9. doi: 10.1016/j.ygyno.2011.02.033.
WHO (2014). Comprehensive cervical cancer control. A guide to essential practice, 12–14.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeThe Effect of Open Access).