Characterization of cervical biopsies of women with HIV and HPV co-infection using p16ink4a, ki-67 and HPV E4 immunohistochemistry and DNA methylation
| Autor: | Wieke W. Kremer, Greta Dreyer, Frederique J Vink, Marjolein van Zummeren, Chris J.L.M. Meijer, Lawrence Rozendaal, Maaike C G Bleeker, John Doorbar |
|---|---|
| Přispěvatelé: | Pathology, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), AII - Cancer immunology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Pathology Cervical intraepithelial neoplasia Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Internal medicine medicine neoplasms biology business.industry HPV infection Cancer virus diseases Methylation medicine.disease female genital diseases and pregnancy complications 030104 developmental biology Dysplasia 030220 oncology & carcinogenesis Ki-67 DNA methylation biology.protein Immunohistochemistry business |
| Zdroj: | Modern Pathology, 33(10), 1968-1978. Nature Publishing Group Kremer, W W, Vink, F J, van Zummeren, M, Dreyer, G, Rozendaal, L, Doorbar, J, Bleeker, M C G & Meijer, C J L M 2020, ' Characterization of cervical biopsies of women with HIV and HPV co-infection using p16ink4a, ki-67 and HPV E4 immunohistochemistry and DNA methylation ', Modern Pathology, vol. 33, no. 10, pp. 1968-1978 . https://doi.org/10.1038/s41379-020-0528-x, https://doi.org/10.1038/s41379-020-0528-x |
| ISSN: | 0893-3952 |
| DOI: | 10.1038/s41379-020-0528-x |
| Popis: | This study aims to characterize cervical intraepithelial neoplasia (CIN) in women living with HIV using biomarkers. Immunohistochemical (IHC) staining for human papillomavirus (HPV) E4 protein indicates CIN with productive HPV infection, whereas Ki-67 and p16ink4a indicate CIN with transforming characteristics, which may be further characterized using DNA hypermethylation, indicative for advanced transforming CIN. Cervical biopsies (n = 175) from 102 HPV positive women living with HIV were independently reviewed by three expert pathologists. The consensus CIN grade was used as reference standard. IHC staining patterns were scored for Ki-67 (0–3), p16ink4a (0–3), and E4 (0–2) and correlated to methylation levels of four cellular genes in corresponding cervical scrapes. Reference standards and immunoscores were obtained from 165 biopsies:15 no dysplasia, 91 CIN1, 31 CIN2, and 28 CIN3. Ki-67 and p16ink4a scores increased with increasing CIN grade, while E4 positivity was highest in CIN1 and CIN2 lesions. E4 positive CIN1 lesions had higher Ki-67 and p16ink4a scores and higher methylation levels compared with E4 negative CIN1 lesions. E4 positive biopsies with low cumulative Ki-67/p16 ink4a immunoscores (0-3) had significantly higher methylation levels compared with E4 negative biopsies. No significant differences in Ki-67 and p16ink4a scores and methylation levels were observed between E4 negative and positive CIN2 or CIN3 lesions. The presence of high methylation levels in scrapes of CIN lesions with IHC characteristics of both productive (E4 positive) and transforming infections (increased Ki-67/p16ink4a expression) in women living with HIV might indicate a rapid aggressive course of HPV infections towards cancer in these women. |
| Databáze: | OpenAIRE |
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