Characterisation of anal intraepithelial neoplasia and anal cancer in HIV-positive men by immunohistochemical markers p16, Ki-67, HPV-E4 and DNA methylation markers.
Adult
Alphapapillomavirus
/ metabolism
Anal Canal
/ metabolism
Anus Neoplasms
/ diagnosis
Biomarkers, Tumor
/ biosynthesis
Carcinoma in Situ
/ diagnosis
Cross-Sectional Studies
Cyclin-Dependent Kinase Inhibitor p16
/ biosynthesis
DNA Methylation
HIV Infections
/ genetics
Homosexuality, Male
/ statistics & numerical data
Humans
Immunohistochemistry
/ methods
Ki-67 Antigen
/ biosynthesis
Male
Oncogene Proteins, Viral
/ biosynthesis
Papillomavirus Infections
/ genetics
Retrospective Studies
anal high-grade squamous intraepithelial lesion
host cell DNA methylation markers
human immunodeficiency virus
human papillomavirus
immunohistochemistry
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 11 2021
15 11 2021
Historique:
revised:
07
06
2021
received:
12
04
2021
accepted:
05
07
2021
pubmed:
27
7
2021
medline:
23
11
2021
entrez:
26
7
2021
Statut:
ppublish
Résumé
Human papillomavirus (HPV)-induced anal intraepithelial neoplasia (AIN, graded 1-3) is highly prevalent in HIV-positive (HIV+) men who have sex with men (MSM), but only a minority of lesions progresses to cancer. Our study aimed to characterise comprehensively anal tissue samples from a cross-sectional series (n = 104) of HIV+ MSM and longitudinal series (n = 40) of AIN2/3 progressing to cancer using different biomarkers. The cross-sectional series consisted of 8 normal, 26 AIN1, 45 AIN2, 15 AIN3 and 10 anal squamous cell carcinoma. Tissue sections were immunohistochemically (IHC) stained for p16 (viral transformation marker), Ki-67 (cellular proliferation marker) and HPV-E4 (viral production marker). We evaluated the expression of IHC markers and compared it with DNA methylation, a marker for malignant transformation. E4 positivity decreased, whereas p16 and Ki-67 scores and methylation marker positivity increased (P values < .001) with increasing severity of anal lesions. Within AIN2, a heterogeneous biomarker pattern was observed concerning E4, p16 and methylation status, reflecting the biological heterogeneity of these lesions. In the longitudinal series, all AIN2/3 and carcinomas showed high p16 and Ki-67 expression, strong methylation positivity and occasional E4 positivity. We earlier showed that high methylation levels are associated with progression to cancer. The observed E4 expression in some AIN2/3 during the course of progression to cancer and absence of E4 in a considerable number of AIN1 lesions make the potential clinical significance of E4 expression difficult to interpret. Our data show that IHC biomarkers can help to characterise AIN; however, their prognostic value for cancer risk stratification, next to objective methylation analysis, appears to be limited.
Identifiants
pubmed: 34310698
doi: 10.1002/ijc.33748
pmc: PMC9292283
doi:
Substances chimiques
Biomarkers, Tumor
0
Cyclin-Dependent Kinase Inhibitor p16
0
Ki-67 Antigen
0
Oncogene Proteins, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1833-1844Informations de copyright
© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Références
Am J Surg Pathol. 2015 Nov;39(11):1518-1528
pubmed: 26379150
Am J Surg Pathol. 2007 Apr;31(4):555-61
pubmed: 17414102
Curr HIV/AIDS Rep. 2015 Mar;12(1):6-15
pubmed: 25644977
J Low Genit Tract Dis. 2020 Jan;24(1):69-74
pubmed: 31860579
Oncol Lett. 2016 Oct;12(4):2389-2394
pubmed: 27698804
Virology. 2013 Oct;445(1-2):80-98
pubmed: 24016539
Int J Cancer. 2021 Aug 1;149(3):707-716
pubmed: 33729551
Am J Clin Pathol. 2021 May 18;155(6):845-852
pubmed: 33210115
Mod Pathol. 2020 Oct;33(10):1968-1978
pubmed: 32249820
Int J Cancer. 2016 Jan 15;138(2):463-71
pubmed: 26219541
Am J Surg Pathol. 2010 Oct;34(10):1449-55
pubmed: 20871219
PLoS One. 2012;7(12):e49974
pubmed: 23226504
Clin Infect Dis. 2021 Jun 15;72(12):2154-2163
pubmed: 32266940
Am J Surg Pathol. 2006 Jul;30(7):795-801
pubmed: 16819320
Arch Pathol Lab Med. 2020 Jun;144(6):725-734
pubmed: 31718233
Acta Pathol Microbiol Immunol Scand A. 1986 Sep;94(5):343-9
pubmed: 3766143
Mol Oncol. 2021 Nov;15(11):3024-3036
pubmed: 33580586
Lancet Oncol. 2012 May;13(5):487-500
pubmed: 22445259
Clin Infect Dis. 2021 Mar 1;72(5):853-861
pubmed: 32342984
Int J Epidemiol. 2017 Jun 1;46(3):924-938
pubmed: 27789668
Mod Pathol. 2015 Jul;28(7):977-93
pubmed: 25953390
Int J Cancer. 2021 Jan 1;148(1):38-47
pubmed: 32621759
J Low Genit Tract Dis. 2012 Jul;16(3):205-42
pubmed: 22820980
Int J Cancer. 2009 May 15;124(10):2375-83
pubmed: 19189402
Int J Cancer. 2001 Apr 15;92(2):276-84
pubmed: 11291057
Nat Rev Cancer. 2014 Jun;14(6):395-405
pubmed: 24854082
J Infect Dis. 2021 Oct 13;224(7):1271-1272
pubmed: 33564850
Epigenetics. 2008 May-Jun;3(3):149-56
pubmed: 18567946
Int J Cancer. 2014 Mar 1;134(5):1147-55
pubmed: 23934991
Br J Dermatol. 2020 Apr;182(4):1026-1033
pubmed: 31302935
Mod Pathol. 2018 Jul;31(7):1026-1035
pubmed: 29434342
Clin Infect Dis. 2019 Mar 19;68(7):1204-1212
pubmed: 30060087
Intervirology. 1993;36(2):57-64
pubmed: 8294182
Am J Surg Pathol. 2018 Apr;42(4):463-471
pubmed: 29438174
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Oncol Lett. 2018 Jan;15(1):11-22
pubmed: 29285184
J Cell Physiol. 1987 Dec;133(3):579-84
pubmed: 3121642
Clin Infect Dis. 2019 Mar 19;68(7):1110-1117
pubmed: 30060049
Int J Cancer. 2021 Nov 15;149(10):1833-1844
pubmed: 34310698
J Clin Pathol. 2018 Nov;71(11):981-988
pubmed: 30012698
Mod Pathol. 2018 Dec;31(12):1842-1850
pubmed: 30135508