Contribution immunochemical methods in diagnosis and prevention of cervical dysplastic changes
Jana Vaculová1, Jaroslav Horáček2
1University Hospital of Ostrava, Department of Pathology, Czech Republic
2University of Ostrava in Ostrava, Faculty of Medicine, Department of Pathology,
Czech Republic
Korespondenční autor: Jaroslav Horáček (jaroslav.horacek@osu.cz)
ISSN 1804-7181 (On-line)
Full verze:
Submitted:16. 4. 2015
Accepted: 9. 6. 2015
Published online: 26. 6. 2015
Summary
Cervical cancer is the world’s fourth most frequent malignancy within the female population. Despite the established screening, incidences in the Czech Republic occur at a rate of about 20 cases per 100,000 women and with a mortality rate around 9 out of 100,000 women. The main factor of dysplasia and subsequent cervical cancer is the chronic infection with the human papillomavirus. This occurs when the oncogenic HPV types inactivate regulatory proteins of a cell and leads to uncontrolled cell proliferation. The aim of this study was to evaluate the benefits of immunochemical methods in the diagnostics of HPV infection in dispensarized patients with a finding of various grades of dysplasia. Immunocytochemical and immunohistochemical methods with an inhibitor of cyclin-dependent kinase p16INK4a and nuclear proliferation marker Ki-67 were used in a sample survey group of 47 women. The sample groups were also tested for the presence of the highly oncogenic HPV types by Hybrid Capture 2 method, but the relationship of the viral load and the grade of dysplasia was not proven. The control group consisted of five patients with normal findings, where the expected negativity of studied markers was confirmed. The results showed a correlation between the expression of the protein p16INK4a in cytological preparations with the morphological manifestations of the HPV infection in histological preparations, particularly with higher grades of dysplastic changes. This work confirmed that the detection of specific markers in the cytological and biopsy material contributes significantly to the specification of the degree of precancerous lesions on the cervix and, thus, their early detection.
Keywords: HPV; p16INK4a; Ki-67; dysplasia; immunohistochemistry; immunocytochemistry; screening
Literatura
1. Agoff SN, Lin P, Morihara J, Mao C, Kiviat NB, Koutsky LA (2003). p16INK4a expression correlates with degree of cervical neoplasia: a comparison with Ki-67 expression and detection of high-risk HPV types. Modern Pathology. 16/7: 665–673.
2. Bergeron C, Ordi J, Schmidt D, Trunk MJ, Keller T, Ridder R, European CINtec Histology Study Group (2010). Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high-grade cervical intraepithelial neoplasia. American Journal of Clinical Pathology. 133/3: 395–406.
3. Cavalcante DM, Linhares IM, Pompeu M, Giraldo PC, Eleutério J (2012). The utility of p16INK4a and Ki-67 to identify high-grade squamous intraepithelial lesion in adolescents and young women. Indian Journal of Pathology and Microbiology. 55/3: 339.
4. del Pino M, Garcia S, Fusté V, Alonso I, Fusté P, Torné A et al. (2009). Value of p16INK4a as a marker of progression/regression in cervical intraepithelial neoplasia grade 1. American Journal of Obstetrics and Gynecology 201/5: 488–e1.
5. Dušková J (2012). Co je nového v cytodiagnostice cervikálních prekanceróz? [What is new in cytodiagnostics of cervical precancerosis?] Česk Patol. 45/1: 22–29 (Czech).
6. Galgano MT, Castle PE, Atkins KA, Brix WK, Nassau SR, Stoler MH (2010). Using biomarkers as objective standards in the diagnosis of cervical biopsies. The American Journal of Surgical Pathology. 34/8: 1077.
7. Gertych A, Anika J, Walts A, Bose S (2012). Automated detection of dual p16/Ki67 nuclear immunoreactivity in liquid-based pap tests for improved cervical cancer risk stratification. Annals of Biomedical Engineering. 40/5: 1192–1204.
8. Globocan (2012). Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. World Health Organization – International Agency for Research on Cancer. [online] [cit. 2015–04–02]. Available at: http://globocan.iarc.fr/…_cancer.aspx
9. Gupta R, Srinivasan R, Nijhawan R, Suri V, Uppal R (2010). Protein p 16INK4A expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix. Indian Journal of Pathology and Microbiology. 53/1: 7.
10. Gustinucci D, Passamonti B, Cesarini E, Butera D, Palmieri Ea, Bulletti S et al. (2012). Role of p16(INK4a) cytology testing as an adjunct to enhance the diagnostic specificity and accuracy in human papillomavirus-positive women within an organized cervical cancer screening program. Acta Cytol. 56/5: 506–514.
11. Horáček J, Kobilková J (2014). Gynekologická cytodiagnostika [Gynecological cytodiagnostics]. Maxdorf (Czech).
12. Iaconis L, Hyjek E, Ellenson L, Pirog E (2007). P16 and Ki-67 immunostaining in atypical immature squamous metaplasia of the uterine cervix. Arch Pathol Lab Med. 131: 1343–1349.
13. Ikenberg H, Bergeron C, Schmidt D, Griesser H, Alameda F, Angeloni C et al. (2013). Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. Journal of the National Cancer Institute. 105/20: 1550–1557.
14. Ma YY, Cheng XD, Zhou CY, Qiu LQ, Chen XD, Lü WG et al. (2011). Value of P16 expression in the triage of liquid-based cervical cytology with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. Chinese Medical Journal. 124/16: 2443.
15. Mikyšková I, Dvořák V, Michal M (2003). Lidské papilomaviry jako příčina vzniku gynekologických onemocnění [Human papillomaviruses as a cause of the emergence of gynecological deseases]. Practical gynecology. 4: 33–36 (Czech).
16. Odile D, Cabay R, Pasha S, Dietrich R, Leach L, Guo M et al. (2009). The role of deeper levels and ancillary studies (p16Ink4a and ProExC) in reducing the discordance rate of Papanicolaou findings of high-grade squamous intraepithelial lesion and follow-up cervical biopsies. Cancer Cytopathology. 117/: 157–166.
17. Ordi J, Sagasta A, Munmany M, Rodríguez-Carunchio L, Torné A et al. (2014). Usefulness of p16/Ki67 immunostaining in the triage of women referred to colposcopy. Cancer Cytopathology. 122/3: 227–235.
18. Pinto AP, Degen M, Villa LL, Cibas ES (2012). Immunomarkers in gynecologic cytology: the search for the ideal ‘biomolecular Papanicolaou test’. Acta Cytologica. 56/2: 109–121.
19. Redman R, Rufforny I, Liu C, Wilkinson EJ, Massoll NA (2008). The utility of p16(Ink4a) in discriminating between cervical intraepithelial neoplasia 1 and nonneoplastic equivocal lesions of the cervix. Archives of Pathology & Laboratory Medicine. 132/5: 795–799.
20. Singh C, Manivel JC, Truskinovsky AM, Slavik K, Amirouche S, Holler J et al. (2014). Variability of pathologists’ utilization of p16 and ki-67 immunostaining in the diagnosis of cervical biopsies in routine pathology practice and its impact on the frequencies of cervical intraepithelial neoplasia diagnoses and cytohistologic correlations. Archives of Pathology & Laboratory Medicine. 138/1: 76–87.
21. van der Marel J, van Baars R, Alonso I, del Pino M, van de Sandt M, Linderman J et al. (2014). Oncogenic Human Papillomavirus – infected Immature Metaplastic Cells and Cervical Neoplasia. The American Journal of Surgical Pathology. 38/4: 470–479.
22. Wentzensen N, Schwartz L, Zuna RE, Smith K, Mathews C et al. (2012). Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population. Clinical Cancer Research. 18/15: 4154–4162.
