Three-tiered score for Ki-67 and p16ink4a improves accuracy and reproducibility of grading CIN lesions
Autor: | Renske D.M. Steenbergen, Annemiek Leeman, Peter J.F. Snijders, Marjolein van Zummeren, Maaike C G Bleeker, Wieke W. Kremer, Chris J.L.M. Meijer, Johannes Berkhof, Daniëlle A.M. Heideman, Miekel M. van de Sandt, David G. Jenkins, Wim Quint |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
HPV Scoring system cervical cancer diagnosis Ki 67 Biopsy Uterine Cervical Neoplasms Cervical intraepithelial neoplasia Pathology and Forensic Medicine Majority consensus 03 medical and health sciences 0302 clinical medicine P16 ink4a Predictive Value of Tests Medicine Humans Grading (tumors) Papillomaviridae Cyclin-Dependent Kinase Inhibitor p16 Retrospective Studies Cervical cancer Observer Variation Reproducibility biology business.industry Papillomavirus Infections Reproducibility of Results General Medicine Reference Standards medicine.disease Uterine Cervical Dysplasia Immunohistochemistry female genital diseases and pregnancy complications 030104 developmental biology Cross-Sectional Studies Ki-67 Antigen 030220 oncology & carcinogenesis Ki-67 biology.protein Original Article Female Neoplasm Grading Nuclear medicine business |
Zdroj: | Journal of Clinical Pathology |
ISSN: | 1472-4146 0021-9746 |
Popis: | AimsTo investigate the accuracy and reproducibility of a scoring system for cervical intraepithelial neoplasia (CIN1–3) based on immunohistochemical (IHC) biomarkers Ki-67 and p16ink4a.Methods115 cervical tissue specimens were reviewed by three expert gynaecopathologists and graded according to three strategies: (1) CIN grade based on H&E staining only; (2) immunoscore based on the cumulative score of Ki-67 and p16ink4a only (0–6); and (3) CIN grade based on H&E supported by non-objectified IHC 2 weeks after scoring 1 and 2. The majority consensus diagnosis of the CIN grade based on H&E supported by IHC was used as the Reference Standard. The proportion of test positives (accuracy) and the absolute agreements across pathologists (reproducibility) of the three grading strategies within each Reference Standard category were calculated.ResultsWe found that immunoscoring with positivity definition 6 yielded the highest proportion of test positives for Reference Standard CIN3 (95.5%), in combination with the lowest proportion of test positives in samples with CIN1 (1.8%). The proportion of test positives for CIN3 was significantly lower for sole H&E staining (81.8%) or combined H&E and IHC grading (84.8%) with positivity definition ≥CIN3. Immunoscore 6 also yielded high absolute agreements for CIN3 and CIN1, but the absolute agreement was low for CIN2.ConclusionsThe higher accuracy and reproducibility of the immunoscore opens the possibility of a more standardised and reproducible definition of CIN grade than conventional pathology practice, allowing a more accurate comparison of CIN-based management strategies and evaluation of new biomarkers to improve the understanding of progression of precancer from human papillomavirus infection to cancer. |
Databáze: | OpenAIRE |
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