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J Cutan Pathol. 2019 Oct;46(10):748-752. doi: 10.1111/cup.13528. Epub 2019 Jul 11.

Cancer-testis antigens as biomarkers for Merkel cell carcinoma: Pitfalls and opportunities.

Author information

1
Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
2
Department of Dermatology, Wayne State University School of Medicine, Detroit, Michigan.
3
Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Abstract

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:

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:

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:

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.

KEYWORDS:

IMP-3; Merkel cell carcinoma; SP-17; TMEFF1; immunohistochemistry

PMID:
31218705
DOI:
10.1111/cup.13528

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