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Abstract：
BACKGROUND: In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage.
METHODS: Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced).
RESULTS: CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients.
CONCLUSIONS: TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.
METHODS: Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced).
RESULTS: CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients.
CONCLUSIONS: TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.
摘要：
背景：在口腔鳞状细胞癌（OSCC）中，肿瘤淋巴结转移(TNM)分期系统是影响OSCC患者预后和治疗决策的重要因素.不幸的是,TNM分期并不能始终预测患者的预后，具有相同临床病理特征的患者可能具有截然不同的生存结果。宿主免疫在肿瘤进展中起重要作用，但不包括在TNM分期系统中。肿瘤浸润淋巴细胞（TIL）是识别肿瘤细胞的宿主免疫反应的一部分；TIL的存在已成为许多类型癌症预后标志物的潜在候选者。本研究旨在确定T细胞特异性标志物（CD3，CD4，CD8和FOXP3）与OSCC患者临床病理特征和生存结果的关系。CD3，CD4和CD8的预后价值也将根据肿瘤分期进行评估。
方法：构建包含231例OSCC的组织微阵列，并通过免疫组织化学染色分析CD3，CD4，CD8和FOXP3的表达。每个标志物的表达评分与临床病理参数和生存结果相关。基于肿瘤分期(早期或晚期)进一步分析CD3、CD4和CD8的预后影响。
结果：使用单变量分析发现CD3、CD4和CD8与总生存期和无进展生存期显著相关。然而,使用多变量分析,没有发现这些标志物能独立预测OSCC的生存结局.只有常规因素，如节点状态，肿瘤分化和神经浸润（PNI）是生存结局的独立预测因子，节点状态是最强的独立预测因子。此外,发现低CD4(而非CD3或CD8)表达可确定预后异常差的早期OSCC患者,这与晚期OSCC患者相似.
结论：TIL标志物如CD3、CD4、CD8和FOXP3可以预测OSCC患者的生存结果，但不能作为常规因素(即淋巴结状态，肿瘤分化和PNI）。CD4表达可能有助于早期OSCC患者的风险分层，这可能会影响早期OSCC患者的治疗计划和决策。
方法：构建包含231例OSCC的组织微阵列，并通过免疫组织化学染色分析CD3，CD4，CD8和FOXP3的表达。每个标志物的表达评分与临床病理参数和生存结果相关。基于肿瘤分期(早期或晚期)进一步分析CD3、CD4和CD8的预后影响。
结果：使用单变量分析发现CD3、CD4和CD8与总生存期和无进展生存期显著相关。然而,使用多变量分析,没有发现这些标志物能独立预测OSCC的生存结局.只有常规因素，如节点状态，肿瘤分化和神经浸润（PNI）是生存结局的独立预测因子，节点状态是最强的独立预测因子。此外,发现低CD4(而非CD3或CD8)表达可确定预后异常差的早期OSCC患者,这与晚期OSCC患者相似.
结论：TIL标志物如CD3、CD4、CD8和FOXP3可以预测OSCC患者的生存结果，但不能作为常规因素(即淋巴结状态，肿瘤分化和PNI）。CD4表达可能有助于早期OSCC患者的风险分层，这可能会影响早期OSCC患者的治疗计划和决策。
