Impact of CD68, CD4, TNF-α, and COX-2 expression on disease-specific survival in Brazilian patients with OSCC.
Sibele Nascimento de Aquino, Lucas Lacerda de Souza, Hélen Kaline Farias Bezerra, Daniel Gomes de Alvarenga, Paulo Rogério Ferreti Bonan, Helder Domiciano Dantas Martins, Alan Roger Santos-Silva, Márcio Ajudarte Lopes, Pablo Agustin Vargas
Abstract
Open AccessOral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck. Studies on the inflammatory pathways that have evolved during the development of the disease remain controversial. We assessed the expression of inflammatory markers, such as COX (cyclooxygenase)-2, CD68, CD4, and tumor necrosis factor (TNF)-α, based on prognostic variables and disease-specific survival in patients with OSCC. Immunohistochemical analysis of COX-2, TNF-α, CD4, and CD68 was conducted in 72 patients treated surgically. Neural invasion was evaluated based on S100 expression. Disease-specific survival was assessed using Cox regression analysis. Most participants were male, with a mean age of 61 years. A total of 77.5% of patients presented with clinical stages III-IV, and 70% underwent surgery combined with radiotherapy or chemotherapy. The expression of CD68, CD4, and TNF-α was not associated with clinical variables or tumor differentiation. COX-2 expression correlated with tumor size (p = 0.01), whereas high TNF-α expression was noted in moderately/poorly differentiated OSCC. The absence of nodal involvement (hazard ratio [HR]: 0.47, confidence interval [CI]: 0.25-0.87, p = 0.001) was linked to lower death risk, whereas surgery without adjuvant radiotherapy or chemotherapy was associated with a higher risk of death (HR: 2.09, 95%CI: 1.02-4.27, p = 0.043). Multivariate analysis revealed that high COX-2 expression predicted a shorter disease-specific survival. Altogether, high TNF-α expression is prevalent in moderately/poorly differentiated OSCC, and elevated COX-2 expression correlates with larger tumor size and poorer survival in OSCC.