Urothelial Carcinoma In Situ of the Bladder: Correlation of CK20 Expression With Adaptive Immune Resistance, Response to BCG Therapy, and Clinical Outcome.
Adult
Aged
Aged, 80 and over
Carcinoma in Situ
/ immunology
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Keratin-20
/ immunology
Male
Middle Aged
Mycobacterium bovis
Neoplasm Proteins
/ immunology
Tumor Escape
Urinary Bladder Neoplasms
/ immunology
Urothelium
/ immunology
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 02 2021
01 02 2021
Historique:
received:
05
06
2020
accepted:
27
07
2020
pubmed:
29
8
2020
medline:
30
10
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Immunohistochemical stains have been suggested to aid in diagnostically challenging cases of urothelial carcinoma in-situ (CIS). Although full thickness immunostaining for CK20 is supportive of CIS, a subset of CIS cases is CK20(-), the clinical significance of which was unknown. This study included 43 patients with primary diagnosis of bladder CIS including 32 with only CIS, 5 with CIS and separate noninvasive high-grade papillary urothelial carcinoma, and 6 with CIS and separate high-grade urothelial carcinoma with lamina propria invasion. Digital morphometric image analysis showed that the average nuclear areas of enlarged nuclei were similar in CK20(+) and CK20(-) CIS (26.9 vs. 24.5 µM2; P=0.31). Average Ki67 index for CK20(+) CIS was higher than CK20(-) CIS (31.1% vs. 18.3%; P=0.03). Patients with CK20(+) CIS [28 (65%)] and patients with CK20(-) CIS [15 (35%)] had the same rates of Bacillus Calmete-Guerin (BCG) failure but patients with CK20(-) CIS had higher stage progression [3 CK20(+) (11%) vs. 6 CK20(-) (40%); P=0.02]. Given recent approval of immune checkpoint inhibitors in patients with CIS refractory to BCG, programmed death ligand-1 expression and colocalization with CD8(+) lymphocytes was investigated as signature of adaptive immune response and was seen in 8 patients regardless of CK20 status and exclusively among patients who failed BCG. Our results confirm that negative CK20 IHC does not exclude CIS and that those patients have similar clinical outcomes as patients with CK20(+) CIS. Programmed death ligand-1 and CD8 colocalization seen among patients who failed BCG therapy is an easy assay to perform to identify patients who could potentially benefit from combined BCG therapy and immune checkpoint inhibition.
Identifiants
pubmed: 32858539
pii: 00129039-202102000-00008
doi: 10.1097/PAI.0000000000000872
pmc: PMC7878196
mid: NIHMS1617607
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
KRT20 protein, human
0
Keratin-20
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
127-135Subventions
Organisme : NIGMS NIH HHS
ID : P50 GM107632
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA193145
Pays : United States
Informations 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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