Adenocarcinoma of the Uterine Cervix: Immunohistochemical Biomarker Expression and Diagnostic Performance.
Adenocarcinoma
/ diagnosis
Alphapapillomavirus
/ physiology
Biomarkers, Tumor
/ metabolism
Carcinoembryonic Antigen
/ metabolism
Cluster Analysis
Cyclin-Dependent Kinase Inhibitor p16
/ metabolism
Female
Humans
Immunohistochemistry
Papillomavirus Infections
/ diagnosis
Receptors, Estrogen
/ metabolism
Uterine Cervical Neoplasms
/ diagnosis
Journal
Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
23
05
2020
accepted:
30
09
2020
pubmed:
3
12
2020
medline:
4
11
2021
entrez:
2
12
2020
Statut:
ppublish
Résumé
Immunohistochemistry (IHC) improves the diagnosis of cervical adenocarcinoma but is not adequately studied. The performance of 16 antibodies previously reported as potentially discriminating between some histotypes was investigated in 184 tumors comprised of 12 histotype groups collapsed into 3 categories [47 adenocarcinomas in situ (AIS), 121 probable human papillomavirus-dependent adenocarcinomas (HPVD), and 16 of probable independence (HPVI)]. IHC sections from 5 tissue microarrays were scanned, and 3 pathologists independently reviewed images to assess staining percentages and intensities. Biomarker expression was based on published positive and negative cutoffs and agreement between any 2 pathologists. Differences between the 3 categories in the hierarchical ranking of biomarker positivity were analyzed by Random Forest classification, and between select groups by Unsupervised Hierarchical Clustering. Important category discriminants were combined in logistic regression models and the area under the curve (AUC) computed. Potential group discriminants were terminal cluster biomarkers with a 50% or more difference in positivity. Strong associations occurred between the lower expression of carcinoembryonic antigen and stromal actin in AIS compared with HPVD [AUC=0.70, 95% confidence interval (CI), 0.59-0.80] and in the higher expression of p16 and estrogen receptor in comparison to HPVI (AUC=0.86, 95% CI, 0.73-0.98), and between the higher expression of p16, carcinoembryonic antigen and estrogen receptor in HPVD compared with HPVI (AUC=0.88, 95% CI, 0.77-0.99). Between select groups, 9 biomarkers emerged as potential discriminants. Select IHC biomarkers can discriminate AIS from invasive adenocarcinomas, and invasive adenocarcinomas stratified by human papillomavirus dependency from each other. Independent replication in larger studies is needed, and to confirm discriminants of histotype groups.
Identifiants
pubmed: 33264105
pii: 00129039-202103000-00006
doi: 10.1097/PAI.0000000000000881
doi:
Substances chimiques
Biomarkers, Tumor
0
CDKN2A protein, human
0
Carcinoembryonic Antigen
0
Cyclin-Dependent Kinase Inhibitor p16
0
Receptors, Estrogen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
209-217Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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