Immunohistochemical expression of p16INK4A in the lesions of uterine cervix
DOI:
https://doi.org/10.21276/APALM.2880Keywords:
p16INK4A, intraepithelial neoplasia, cervix carcinomaAbstract
Background: Cervical cancer is the major cause of cancer deaths among women. Globally, around 5,70,000 new cases of cervical cancer and 3,11,000 deaths occurred in the year 2018. In India, Cervical cancer is a leading cause of cancer related mortality among women and the number of deaths is 60,000 per year among 97,000 diagnosed patients, especially those from lower socioeconomic group. Human Papilloma Virus (HPV) plays a crucial role in causing cervical dysplasia. This is done by upregulating p16INK4A, a cyclin dependent kinase inhibitor through interaction with cellular regulatory proteins. Hence p16INK4A can be used as a biomarker, since it is directly related variable for the presence of HPV. This study was conducted to evaluate the expression of p16INK4A in benign, premalignant and malignant cervical lesions and to assess its utility in diagnosing and grading cervical lesions.
Methods: A total of 80 cervical specimens categorized histopathologically into nonspecific cervicitis, low grade squamous intraepithelial neoplasia (LSIL), high grade squamous intraepithelial neoplasia (HSIL) and squamous cell carcinoma cervix were included in this prospective study of one-year duration. Immunohistochemical study of p16INK4A were interpreted qualitatively and semi-quantitatively by Allred scoring system (0 to 8 points) which measures the proportion of stained cells and intensity of staining of cells. The collected data were statistically analyzed by ANOVA and chi square test.
Result: Qualitative method showed absence of p16INK4A expression in all nonspecific cervicitis. 16.7% (2/12) LSIL, 100% (12/12) HSIL and 100% (28/28) squamous cell carcinoma cases showed p16INK4A positivity. Allred scoring of p16INK4A showed 66% (8/12) HSIL and 85.7% (24/28) squamous cell carcinoma cases with score 3 positivity. Hence high-grade lesions showed higher expression of this marker.
Conclusion: IHC expression of p16INK4A showed increasing degree of expression from benign to premalignant and malignant lesions suggesting its diagnostic and prognostic value in the cervical cancer management
References
2. Kaarthigeyan K.Indian J med Paediatr Oncol.2012 Jan-Mar;33(1):7-12.
3. Denny L. Cervical cancer: prevention and treatment.Discov Med.2012;14:125-131
4. Schiffman M,Castle PE,Jeronimo J,et al:Human papilloma virus and cervical cancer.Lancet 370:890,2007
5. Queiroz C, Silva TC, Alves VAF, et al. P16(INK4a) expression as potential prognostic marker in cervical pre- neoplastic and neoplastic lesions. Pathol Pract Res 2006; 202: 77- 83.
6. Keating JT, Cviko A, Riethdorf S, et al. Ki-67, cyclin E, and p16INK4 are complementary surrogate biomarkers for human papillomavirus related cervical neoplasia. Am J Surg Pathol 2001; 25(7): 884-91.
7. Jiang, et al. Prognostic value of p16 expression in Epstein Bar Virus positive nasopharyngeal carcinomas. Head Neck. 2016 Apr
8. Branca M, Ciotti M, Santini D, et al. P16 (INK4A) expression is related to grade of cin and high-risk human papillomavirus but does not predict virus clearance after conization or disease outcome. Int J Gynecol Pathol 2004; 23(4): 354-65.
9. Bahnassy AA, Zekri ARN, Saleh M, Lotayef M, Moneir M, Shawki O. The possible role of cell cycle regulators in multistep process of HPVassociated cervical carcinoma. BMC Clin Pathol 2007; 7: 4.
10. George L.Mutter,Jaime Prat., “Cervical benign and non neoplastic lesions,†Pathology of the female genital tract,2 nd edition, pp. 170,2009.
11. George L.Mutter,Jaime Prat., “ Biology of cervical squamous neoplasia,†Pathology of the female genital tract,2 nd edition, pp. 191,2009.
12. Well M,Ostor AG,Franceshi S et al.Epithelial tumours of the uterine cervix.In: Tavassoli FA,Devilee P,editors.Tumors of the breast and female genital organs.LONS,France:IARC Press;2003.p.221-32.
13. Mahdieh Farzanehpour et al. P16INK4A Immunohistochemistry as a Gold standard for Cervical Cancer and Precursor Lesions Screening Iran J Public Health, Vol. 49, No.2, Feb 2020, pp.312-322
14. Miriam Reuschenbach1, Mirjam Seiz1, Christina von Knebel Doeberitz1, Svetlana Vinokurova1, Alexander Duwe2,Ruediger Ridder2, Heike Sartor1, Friedrich Kommoss3, Dietmar Schmidt3 and Magnus von Knebel Doeberitz, Evaluation of cervical cone biopsies for coexpression
a. of p 16INK4a and Ki-67 in epithelial cells, Int. J. Cancer: 130, 388–394 (2012).
15. S. Nicholas Agoff, M.D., Patricia Lin, M.P.H., Janice Morihara, B.S., Constance Mao, M.D.,Nancy B. Kiviat, M.D., Laura A. Koutsky, Ph.D: p16INK4a Expression Correlates with Degree of Cervical Neoplasia. A Comparison with Ki-67 Expression and Detection of High-Risk HPV Types Mod Pathol 2003;16(7):665–673.
16. Fatemeh Sari Aslani et al. Cell cycle and/or proliferation markers:What is the best method to discriminate cervical high-grade lesions,Hum Pathol 2005; 36 : 1101-7.
17. Hu L, Guo M, He Z, Thornton J, Mcdaniel LS, Hughson MD. Human papilloma virus genotyping and p16ink4a expression in cervical intraepithelial neoplasia of adolescents. Mod Pathol. 2005;18:267–73
18. Kishore, Vatsala, and Anuradha G Patil. “Expression of p16INK4A Protein in Cervical Intraepithelial Neoplasia and Invasive Carcinoma of Uterine Cervix.†Journal of clinical and diagnostic research : JCDR vol. 11,9 (2017): EC17-EC20. doi:10.7860/JCDR/2017/29394.10644
19. Natália Gaspar Munhoz, Damaris Aparecida Rodrigues et al, The Use of Molecular Markers (p16, Ki-67 and E-Cadherin) in Uterine Cervical Biopsies, The Open Pathology Journal, 2009, 3, 10-17.
20. Benevolo M, Mottolese M, Marandino F, et al. Immunohistochemical expression of p16(INK4a) is predictive of HR-HPV infection in cervical low-grade lesions. Mod Pathol 2006; 19(3): 384-91.
21. Volgareva G, Zavalishina L, Andreeva Y, et al. Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells. BMC Cancer 2004; 4: 58.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2020 Niharika Rawat, Shivapriya Rajan
This work is licensed under a Creative Commons Attribution 4.0 International 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 (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).