Track: Basic Science

Abstract:

Introduction: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer linked to sun exposure or Merkel cell polyomavirus (MCPyV) association.
Objective: Assessing immunohistochemistry (IHC) for PKCε, PD-L2, GLI-1, SHH, p53, IFN-γ, RhoA, RhoC, STAT3, AKT, TNF-α, and MCPyV in MCC biopsies, focusing on the MCPyV and sun-exposure associations.
Methods: In this IRB-approved retrospective study, 27 MCC specimens were evaluated. Two dermatopathologists independently scored IHC on a 0–4 scale for staining intensity and extent.
Results: Most patients were women (15/27, 55.6%), with 74.1% (20/27) of tumors in sun-exposed sites. MCPyV was detected in 63% (17/27), with no significant difference between sun-exposed and non-exposed areas (13/20 vs. 4/7; p=1). All tumors expressed RhoC, STAT3, and AKT-1 (average 2.3–3.5), while RhoA and PD-L2 were positive in 92.6% (25/27). MCPyV-positive tumors showed higher RhoA (3.5 vs. 2.3; p=0.003), AKT-1 (3.4 vs. 2.3; p=0.018), and PKCε (3.1 vs. 1.0; p<0.001). RhoA was also elevated in sun-exposed tumors (3.1 vs. 2.4; p=0.013). IFN-γ was low in both groups (1.6–2.2; p=0.279). TNF-α and p53 were modest (<1.0), and GLI-1 and SHH were negative.
Discussion: Global geographic factors may influence MCPyV behavior in MCC. PD-L2 positivity in both viral and sun-driven tumors indicates shared-immune evasion. PKCε, RhoA, and AKT prominence in MCPyV-positive cases suggests therapeutic relevance, with RhoA also consistently elevated in sun-driven tumors.
Conclusion: Geographic factors may shape MCPyV behavior in MCC. RhoA and PKCε may represent distinct targetable pathways, respectively linked to sun-damage and viral signaling.

Gustavo Engelman

Affiliation

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(476) Merkel Cell Carcinoma: New Pathogenic Highlights on the MCPyV- and Sun-Driven Pathways