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Updated: Sep 2, 2025
Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel cell carcinoma
Sujatha Muralidharan1,2, Thibault Kervarrec3,2, Glen J Weiss1
1SOTIO Biotech Inc., Cambridge, MA 02140, USA.
Introduction:
Merkel cell carcinoma (MCC) is an aggressive skin cancer, related to the Merkel Cell Polyomavirus (MCPyV) in 80% of cases. Immune checkpoint inhibitors provide sustained benefit in about 50% of MCC patients with advanced disease. Glypican-3 (GPC3) is an oncofetal tumor antigen that is an attractive target for chimeric antigen receptor T cell therapy due to its highly restricted expression on normal tissue and high prevalence in several solid tumors. GPC3 is known to be expressed in MCC but its association with tumor characteristics or prognosis has not been reported. We investigated MCC GPC3 expression by immunohistochemistry (IHC) and its association with tumor characteristics, MCPyV status, and patient outcome.
Methods:
The GC33 antibody clone was validated for GPC3 IHC staining of tumor specimens in comparison to an established GPC3 IHC antibody. An MCC tissue microarray was stained for GPC3 by IHC using GC33 antibody. Association of GPC3+ IHC with baseline characteristics, MCPyV status (qPCR) and outcome (death from MCC/recurrence) were assessed.
Results:
Forty-two of 62 samples (67.7%) were GPC3+. GPC3 expression was more frequently observed in females (p = 0.048) and MCPyV-negative tumors (p = 0.021). By multivariate analysis, GPC3 expression was associated with increased death from disease (CSS) (hazard ratio [HR] 4.05, 95% CI 1.06-15.43), together with advanced age (HR 4.85, 95% CI 1.39-16.9) and male gender (HR 4.64, 95% CI 1.31-16.41).
Conclusions:
GPC3 expression is frequent in MCC tumors, especially MCPyV-negative cases, and is associated with increased risk of death. High prevalence of surface GPC3 makes it a putative drug target.
Insights
Glypican-3 (GPC3) is frequently expressed in Merkel cell carcinoma (MCC), particularly in virus-negative cases. GPC3 expression in MCC is linked to a higher risk of mortality, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Merkel cell carcinoma (MCC) is an aggressive skin cancer, with 80% of cases linked to Merkel Cell Polyomavirus (MCPyV).
- Immune checkpoint inhibitors offer sustained benefits for approximately 50% of advanced MCC patients.
- Glypican-3 (GPC3) is an oncofetal antigen with restricted normal tissue expression, making it a promising target for chimeric antigen receptor T cell therapy.
Purpose of the Study:
- To investigate Glypican-3 (GPC3) expression in Merkel cell carcinoma (MCC) using immunohistochemistry (IHC).
- To assess the association of GPC3 expression with MCC tumor characteristics, MCPyV status, and patient outcomes.
- To evaluate GPC3 as a potential therapeutic target for MCC.
Main Methods:
- Validated the GC33 antibody clone for GPC3 IHC staining.
- Stained an MCC tissue microarray for GPC3 using IHC.
- Assessed the association of GPC3 positivity with baseline characteristics, MCPyV status (qPCR), and patient outcomes (death from MCC/recurrence).
Main Results:
- GPC3 expression was observed in 67.7% of MCC samples.
- GPC3 positivity was more frequent in females and MCPyV-negative tumors.
- Multivariate analysis indicated GPC3 expression is associated with increased cancer-specific survival risk, alongside advanced age and male gender.
Conclusions:
- GPC3 is frequently expressed in MCC, particularly in MCPyV-negative tumors.
- GPC3 expression in MCC is associated with an increased risk of death.
- The high prevalence of surface GPC3 suggests its potential as a drug target for MCC therapy.
