Prognostic Value of KI6 Biomarker in Predict Short Time Prognosis of Low Grade Cervical Intraepithelial Neoplasia in HPV Negative and Positive Patients

  • Leila Mousavi Seresht Department of Obstetrics and Gynecology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Noorieh Sharifi Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Helena Azimi Department of Obstetrics and Gynecology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Nooshin Babapour Department of Obstetrics and Gynecology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Zohreh Yousefi Mail Department of Obstetrics and Gynecology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Mona Najafi Department of Socio-Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Keywords:
KI-67 biomarker, HPV infection prognosis, Cervical intraepithelial neoplasia, Immunohistochemistry

Abstract

Screening of cervical cancer is the most common gynecologic cancer in developing countries. Despite being preventable, but we have still some problems with the screening of this cancer. Recently, many studies have been done on immunohistochemistry to improve screening of cervical intraepithelial neoplasia (CIN) as a precancerous lesion. But, the majority of the studies are based on cytological samples. The objective of this study was to analyze the correlation KI-67 biomarker and HPV infection in predict short time prognosis in CIN as an alternative or auxiliary method to the current screening method in a different geographic population. This descriptive cohort prospective study included 40 patients with a diagnosis of CIN based on cervical punch biopsy samples after colposcopy examination. They were referred to the department of gynecology and oncology of an academic hospital, Mashhad University of   2016 to 2017. All samples were investigated for HR- HPV DNA with Cobas test and immunostaining for KI-67 biomarker. Finally, after one year follows up, the prognosis for all patients was evaluated. Data were analyzed by SPSS software program version 23.0 and Mann-Whitney U test and Fisher's exact test. P<0.05 was considered significant. Significant difference was found between HR-HPV positive and negative tests in KI-67 expression (P<0.001), but no significant difference was observed in reactivity level (P=0.5), also no significant difference was found in KI-67 expression in the metaplastic and non-metaplastic epithelium (P=0.88). KI-67 biomarker is recommended as complementary screening tests not alternative for differentiating in high risks patients with CIN1. The patients with low KI-67 / HR-HPV positive test could be offered for a less aggressive follow-up protocol.

References

1. Kanthiya K, Khunnarong J, Tangjitgamol S, Puripat N, Tanvanich S. Expression of the p16 and KI-67 in Cervical Squamous Intraepithelial Lesions and Cancer. Asian Pac J Cancer Prev 2016;17:3201-6.
2. Possati-Resende JC, Fregnani JH, Kerr LM, Mauad EC, Longatto-Filho A, Scapulatempo-Neto C. The Accuracy of p16/KI-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL. PloS One 2015;10:e0134445.
3. Alshenawy HA. Evaluation of p16, human papillomavirus capsid protein L1 and KI-67 in cervical intraepithelial lesions: Potential utility in diagnosis and prognosis. Pathol Res Pract 2014;210:916-21.
4. Korolczuk A, Orzel M, Wozniak S, Smolen A, Caban K. P16/KI-67 Dual immunostaining in conventional cytology in women with positive papanicolau test. J Cytol Histol 2015;6:1.
5. Luttmer R, Dijkstra MG, Snijders PJ, Berkhof J, van Kemenade FJ, Rozendaal L, et al. p16/KI-67 dual-stained cytology for detecting cervical (pre) cancer in a HPV-positive gynecologic outpatient population. Mod Pathol 2016;29:870-8.
6. Wentzensen N, Schwartz L, Zuna RE, Smith K, Mathews C, Gold MA, et al. Performance of p16/KI-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population. Clin Cancer Res 2012;18:4154-62.
7. Rossi P, Borghi L, Ferro R, Mencarelli R. A population of 1136 HPV DNA-HR positive women: expression of p16 (INK4a)/KI-67 dual-stain cytology and cytological diagnosis. Histological correlations and cytological follow up. Pathologica 2015;107:185-91.
8. Dellas A, Schultheiss E, Almendral AC, Torhorst J, Gudat F. Assessment of EGFR and TGF‐alpha expression in relationship to HPV status and KI‐67 distribution in cervical intraepithelial neoplasms. Int J Cancer 1996;69:165-9.
9. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. Cancer J Clin 2011;61:69-90.
10. Gustinucci D, Giorgi Rossi P, Cesarini E, Broccolini M,Bulletti S, Carlani A, et al. Use of Cytology, E6/E7 mRNA, and p16INK4a-KI-67 to Define the Management of Human Papillomavirus (HPV)-Positive Women in Cervical Cancer Screening. Am J Clin Pathol 2016;145:35-45.
11. Solares C, Velasco J, Alvarez-Ruiz E, Gonzalez-Fernandez L, Encinas AI, Astudillo A, et al. Expression of p16/KI-67 in ASC-US/LSIL or Normal Cytology with Presence of Oncogenic HPV DNA. Anticancer Res 2015;35:6291-5.
12. Heideman DA, Hesselink AT, Berkhof J, van Kemenade F, Melchers WJ, Daalmeijer NF, et al. Clinical validation of the cobas® 4800 HPV Test for cervical screening purposes. J Clin Microbiol 2011;49:3983-5.
13. cobas® 4800 HPV Test [package insert, CE]. Branchburg, NJ: Roche Molecular Systems, Inc; 2012. (Accessed June 2018, 12, at https://www.accessdata.fda.gov/cdrh_docs/ pdf10/p100020s017c.pdf).
14. Lim S, Lee MJ, Cho I, Hong R, Lim SC. Efficacy of p16 and KI-67 immunostaining in the detection of squamous
intraepithelial lesions in a high-risk HPV group. Oncol Lett 2016;11:1447-52.
15. White C, Bakhiet S, Bates M, Keegan H, Pilkington L, Ruttle C, et al. Triage of LSIL/ASC‐US with p16/Ki‐67 dual staining and human papillomavirus testing: a 2‐year prospective study. Cytopathology 2016;27:269-76.
16. Ancuta E, Ancuta C, Cozma LG, Iordache C, Anghelache-Lupascu I, Anton E, et al. Tumor biomarkers in cervical cancer: focus on KI-67 proliferation factor and E-cadherin expression. Rom J Morphol Embryol 2009;50:413-8.
17. Scholzen T, Gerdes J. The Ki‐67 protein: from the known and the unknown. J Cell Physiol 2000;182:311-22.
18. Šekoranja D, Fokter AR. Triaging Atypical Squamous Cells—Cannot Exclude High-Grade Squamous Intraepithelial Lesion With p16/Ki67 Dual Stain. J Low Genit Tract Dis 2017;21:108-11.
19. Schmidt D, Bergeron C, Denton KJ, Ridder R. p16/ki‐67 dual‐stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology. Cancer Cytopathol 2011;119:158-66.
Published
2019-01-15
How to Cite
1.
Mousavi Seresht L, Sharifi N, Azimi H, Babapour N, Yousefi Z, Najafi M. Prognostic Value of KI6 Biomarker in Predict Short Time Prognosis of Low Grade Cervical Intraepithelial Neoplasia in HPV Negative and Positive Patients. Acta Med Iran. 56(11):692-697.
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Articles