Role of P16INk4a And Ki-67 Immunostaining as Specific Biomarker of Cervical Intraepithelial Lesions among Cervical Biopsy Samples: A Diagnostic Study
Authors/Creators
- 1. Resident, Department of Pathology, Dr SN Medical College, Jodhpur
- 2. Ex.HOD and Senior Professor, Department of Pathology, Dr SN Medical College, Jodhpur
- 3. Senior Resident, Department of Pathology, Dr SN Medical College, Jodhpur
- 4. Senior Resident, Department of Surgery, Dr SN Medical College, Jodhpur
Description
Introduction: Cervical carcinoma, fourth most common cancer among women globally. The diagnosis on histopathology is considered as gold standard ,but pathologist faces diagnostic dilemmas not only because of overlap in morphological features among different grades of CIN but also due to intero bserver and intrao bserver variability especially during grading of CIN which affect the prognosis of the patient. For the prognostication and grading of tumours ,an application of IHC marker p16 and proliferative marker like Ki67 become imperative. Aim: Role of p16ink4a and ki-67 immunostaining as specific biomarker of cervical intraepithelial lesions among cervical biopsy samples. Method: Paraffin block of cases that fulfilled the inclusion criteria will be selected. Issued blocks will be cut serially at 3 to 5-micron thickness using rotatory microtome to prepare slides. Slides will be stained with routine hematoxylin and eosin stain and then mounted with DPX to review, after confirming and noting the diagnosis and microscopy details, sections will be taken for P16INK4a and Ki-67 staining. Results: According to P16 IHC 72.86% of cases shows positive expression followed by 7.14% shows equivocal expression and remaining 20% cases shows negative expression. .According to Ki-67 IHC 78.57% cases shows positive expression and 21.43% cases shows negative expression . P16 IHC is 100% sensitive, 85.71% specific and 95.59% accurate in predicting positive results among cervical lesions. Ki-67 IHC is 96.49% sensitive, 92.31% specific and 95.71% accurate in predicting positive results among cervical lesions. P16 IHC and Ki-67 IHC shows almost perfect agreement in diagnosis malignant lesion among cervical biopsies with kappa value of 0.951. Conclusion: Ki-67 and p16/INK4a can be used as complimentary tests for differentiating dysplastic and nondysplastic lesions. They also help in confirming the diagnosis in these cases as different lesions have specific treatment protocols based on the degree of dysplasia. The importance of p16/INK4a in cervix is that it is specific for HR-HPV associated dysplasia and is seen in high-grade lesions and few low-grade lesions with high tendency to progress to a higher grade.
Abstract (English)
Introduction: Cervical carcinoma, fourth most common cancer among women globally. The diagnosis on histopathology is considered as gold standard ,but pathologist faces diagnostic dilemmas not only because of overlap in morphological features among different grades of CIN but also due to intero bserver and intrao bserver variability especially during grading of CIN which affect the prognosis of the patient. For the prognostication and grading of tumours ,an application of IHC marker p16 and proliferative marker like Ki67 become imperative. Aim: Role of p16ink4a and ki-67 immunostaining as specific biomarker of cervical intraepithelial lesions among cervical biopsy samples. Method: Paraffin block of cases that fulfilled the inclusion criteria will be selected. Issued blocks will be cut serially at 3 to 5-micron thickness using rotatory microtome to prepare slides. Slides will be stained with routine hematoxylin and eosin stain and then mounted with DPX to review, after confirming and noting the diagnosis and microscopy details, sections will be taken for P16INK4a and Ki-67 staining. Results: According to P16 IHC 72.86% of cases shows positive expression followed by 7.14% shows equivocal expression and remaining 20% cases shows negative expression. .According to Ki-67 IHC 78.57% cases shows positive expression and 21.43% cases shows negative expression . P16 IHC is 100% sensitive, 85.71% specific and 95.59% accurate in predicting positive results among cervical lesions. Ki-67 IHC is 96.49% sensitive, 92.31% specific and 95.71% accurate in predicting positive results among cervical lesions. P16 IHC and Ki-67 IHC shows almost perfect agreement in diagnosis malignant lesion among cervical biopsies with kappa value of 0.951. Conclusion: Ki-67 and p16/INK4a can be used as complimentary tests for differentiating dysplastic and nondysplastic lesions. They also help in confirming the diagnosis in these cases as different lesions have specific treatment protocols based on the degree of dysplasia. The importance of p16/INK4a in cervix is that it is specific for HR-HPV associated dysplasia and is seen in high-grade lesions and few low-grade lesions with high tendency to progress to a higher grade.
Files
IJPCR,Vol15,Issue6,Article175.pdf
Files
(453.2 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:b12cdbf11c5fb7ac9109f9749e002402
|
453.2 kB | Preview Download |
Additional details
Dates
- Accepted
-
2023-06-17
Software
- Repository URL
- https://impactfactor.org/PDF/IJPCR/15/IJPCR,Vol15,Issue6,Article175.pdf
- Development Status
- Active
References
- 1. Colposcopy and treatment of cervical intraepithelial neoplasia: a beginners' manual, Edited by J.W. Sellors and R. Sankaranarayanan. Chapter 2: An Introduction to Cervical Intraepithelial Neoplasia (CIN). 2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021:71:209–49. 3. Dillner J, Rebolj M, Birembaut P, Petry KU, Szarewski A, Munk C, et al. Long Term Predictive Values of Cytology and Human Papillomavirus Testing in Cervical Cancer Screening: Joint European Cohort Study. BMJ. 2008; 337: a1754 4. Sun H, Shen K, Cao D. Progress in immunocytochemical staining for cervical cancer screening. Cancer Manag Res. 2019 Feb 22;11:1817-1827 5. Adetona AE, Ogun GO, Okolo CA, Ogunbiyi JO. 16/Ink4a And Ki-67 Evaluation Of Intraepithelial And Benign Cervical Lesions At The University College Hospital, Ibadan - A Retrospective ImmunohistochemicalStudy. Journal Of Cancer Genetics And Biomarkers.2017;1(2):15-23. 6. Ikenberg H, Bergeron C, Schmidt D, et al. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the palms study. J Natl Cancer Inst. 2013;105(20):1550– 155. 7. Sathiyamurthy K, Waheeda S, Sangeetha N. Histopathological study of cervical lesions in a tertiary health care centre in south India. IJPO. 2021 Nov 28;8(4):447–51. 8. Thirukumar M, Ahilan S. Histopathological Study of Cervical Lesions : A Hospital Based Study in Teaching Hospital Batticaloa. Jaffna Med J. 2020;32(2):34–9. 9. Ezejiofor IF, et al. Histopathological Evaluation of Cervical Lesions in Tertiary Based Hospital with Review of Literatures. Ann Med Health Sci Res. 2021;11:1418-1423. 10. Juan CF, Wright TC, JrAmezcua CA. Cervix in: Modern surgical pathology, (2nd edn) Weidner N (Ed.). Saunders Elsevier, Philadelphia, PA: 2009;1263- 1290. 11. Das D, Sengupta M, Basu K, Tirkey M, Datta C, Chatterjee U. Role of p16/Ki67 Dual immunostaining in detection of cervical cancer precursors. J Cytol. 2018;35(3):153 12. Sripathi DS, Mamatha DM, Akarapu DJD, Pyla DRD. Histomorphological evaluation of cervical punch biopsies with the aid of P16 INK4A and KI 67. Clinical Medicine. 2022;09(06). 13. Waldstrøm M, Christensen RK, Ørnskov D. Evaluation of p16 INK4a /Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion: p16 INK4a /Ki-67 Dual Staining in LSIL. Cancer Cytopathology. 2013 Mar;121(3):136–45.