Cancer-testis antigens as biomarkers for Merkel cell carcinoma: Pitfalls and opportunities.
IMP-3
Merkel cell carcinoma
SP-17
TMEFF1
immunohistochemistry
Journal
Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
24
07
2018
revised:
21
05
2019
accepted:
14
06
2019
pubmed:
21
6
2019
medline:
7
2
2020
entrez:
21
6
2019
Statut:
ppublish
Résumé
The prognosis and treatment options for metastatic Merkel cell carcinoma (MCC) are poor. The immune-privileged status of cancer-testis (CT) antigens imparts tumor specificity, making them ideal candidates for targeted immunotherapy. We investigate the usefulness of the CT antigens SPA17 (sperm protein-17 [SP-17]), IGF2BP3 (insulin-like growth factor-II mRNA-binding protein 3 [IMP-3]), and transmembrane protein with epidermal growth factor (EGF)-like and two follistatin-like domains 1 (TMEFF1) as potential MCC biomarkers and evaluate their possible utility in immunotherapy and molecularly targeted image-guided treatment. The CT antigens SP-17, IMP-3, and TMEFF1 were selected using transcriptome profiling to identify CT antigens expressed in MCC tumors. Antibodies directed against these CT antigens were stained. Twelve normal skin tissue samples were used as a control. The average percentage of positive cells in each tumor was computed. Twelve of 14 (86%) MCC cases showed crisp nuclear staining for SP-17, with 2.06% of cells staining positive. IMP-3 showed crisp, perinuclear staining in all 14 MCC cases, with 52.93% MCC cells staining positive. TMEFF1 showed perinuclear staining in all 14 MCC cases, with 96.51% of tumor cells staining positive. CT antigens were found to be expressed in both MCC and some control tissues. SP-17 was the most specific yet the least sensitive. IMP-3 and TMEFF1 were both sensitive but not specific. CT antigens may represent valuable treatment targets in MCC.
Sections du résumé
BACKGROUND
BACKGROUND
The prognosis and treatment options for metastatic Merkel cell carcinoma (MCC) are poor. The immune-privileged status of cancer-testis (CT) antigens imparts tumor specificity, making them ideal candidates for targeted immunotherapy. We investigate the usefulness of the CT antigens SPA17 (sperm protein-17 [SP-17]), IGF2BP3 (insulin-like growth factor-II mRNA-binding protein 3 [IMP-3]), and transmembrane protein with epidermal growth factor (EGF)-like and two follistatin-like domains 1 (TMEFF1) as potential MCC biomarkers and evaluate their possible utility in immunotherapy and molecularly targeted image-guided treatment.
METHODS
METHODS
The CT antigens SP-17, IMP-3, and TMEFF1 were selected using transcriptome profiling to identify CT antigens expressed in MCC tumors. Antibodies directed against these CT antigens were stained. Twelve normal skin tissue samples were used as a control. The average percentage of positive cells in each tumor was computed.
RESULTS
RESULTS
Twelve of 14 (86%) MCC cases showed crisp nuclear staining for SP-17, with 2.06% of cells staining positive. IMP-3 showed crisp, perinuclear staining in all 14 MCC cases, with 52.93% MCC cells staining positive. TMEFF1 showed perinuclear staining in all 14 MCC cases, with 96.51% of tumor cells staining positive.
CONCLUSIONS
CONCLUSIONS
CT antigens were found to be expressed in both MCC and some control tissues. SP-17 was the most specific yet the least sensitive. IMP-3 and TMEFF1 were both sensitive but not specific. CT antigens may represent valuable treatment targets in MCC.
Identifiants
pubmed: 31218705
doi: 10.1111/cup.13528
pmc: PMC8130841
mid: NIHMS1693993
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
748-752Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC011394
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011450
Pays : United States
Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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