Oncotarget

Research Papers:

Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel cell carcinoma

Sujatha Muralidharan, Thibault Kervarrec, Glen J. Weiss _ and Mahtab Samimi _

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Abstract

Sujatha Muralidharan1,*, Thibault Kervarrec2,*, Glen J. Weiss1 and Mahtab Samimi2

1 SOTIO Biotech Inc., Cambridge, MA 02140, USA

2 Department of Dermatology, University Hospital of Tours, Tours 37170, France

* These authors contributed equally to this work

Correspondence to:

Glen J. Weiss, email: weiss@sotio.com
Mahtab Samimi, email: mahtab.samimi@univ-tours.fr

Keywords: Merkel cell carcinoma; glypican-3; Merkel cell polyomavirus; outcome

Received: June 04, 2022     Accepted: July 12, 2022     Published: August 03, 2022

Copyright: © 2022 Muralidharan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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.


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