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  • br DATA ANALYSIS br All statistical analyses were performed

    2020-08-30


    DATA ANALYSIS
    All statistical analyses were performed using SPSS 13.0 for Windows (SPSS, Inc, Chicago, IL). The associ-ation between CCR4 expression and clinicopathologic features was analyzed by the Pearson c2 test. The Kaplan-Meier method was used to draw survival curves that were compared by log-rank tests. A Cox proportional hazard regression model was used for DFS and OS analyses, and statistically relevant factors in the univariate analysis were included in the multi-variate model analysis. The accepted level of signifi-cance was a P value less than .05.
    Results
    EXPRESSION OF CCR4 IN PRIMARY TONGUE CARCINOMA TISSUES
    CCR4 expression in 128 human tongue cancerous tissues (109 TSCCs and 19 other types) and 10 normal tongue tissues was investigated by IHC. Overall, cell membrane and cytoplasmic staining was observed in cancer cells, followed by confirmation of the speci-
    CCR4 EXPRESSION IN pN0 ORAL TONGUE CANCER
    ficity for CCR4 staining using normal rabbit immuno-globulin G controls (Fig 1Aa). In Leupeptin to weak or absent expression of CCR4 in normal tongue tissues (Fig 1Ab), high levels of positive CCR4 staining were detected in all pathologic types of tongue tumor tis-sues, except adenocarcinoma and sarcoid carcinoma (Fig 1Ac-h, B, Table1).
    CORRELATION BETWEEN CCR4 EXPRESSION AND CLINICOPATHOLOGIC FEATURES
    Patients with SCC were categorized into CCR4-negative (39 cases) and CCR4-positive (70 cases) groups. As presented in Table 2, CCR4-positive expres-sion was significantly correlated with tumor stage (P < .05), but there was no significant difference be-tween CCR4 expression and other clinical parameters, such as gender, age, tobacco history, and histopatho-logic grade (Table 2).
    CORRELATION BETWEEN CCR4 EXPRESSION AND SURVIVAL OF PATIENTS WITH TSCC
    FIGURE 1. Expression of CCR4 in human tongue tumor tissues. A, CCR4 immunohistochemical staining of tongue squamous cell carcinoma and normal tongue tissues. Tongue squamous cell carcinoma tissues showed a, negative ( ), c, d, weak (+), e, f, moderate (++), and g, h, strong
    (+++) staining intensities. b, Normal tongue tissue showed very weak staining ( ). B, CCR4-positive staining was observed in other pathologic types of tongue carcinoma, including a, basal cell adenocarcinoma, b, epithelial-myoepithelial carcinoma, c, adenoid cystic carcinoma, d, mucous epidermoid carcinoma, and e, pleomorphic adenoma. Abbreviation: CCR4, chemokine (C-C motif) receptor-4.
    Wang et al. CCR4 Expression in pN0 Oral Tongue Cancer. J Oral Maxillofac Surg 2019.
    Table 1. IMMUNOHISTOCHEMICAL EXPRESSION OF CCR4
    Epithelial-myoepithelial 1 of 5 (20)
    carcinoma
    Mucous epidermoid carcinoma 2 of 4 (50)
    Abbreviation: CCR4, chemokine (C-C motif) receptor-4.
    Wang et al. CCR4 Expression in pN0 Oral Tongue Cancer. J Oral Maxillofac Surg 2019.
    Kaplan-Meier analysis and log-rank test showed that the OS and DFS of patients with CCR4-positive expres-sion were significantly lower than those of patients with CCR4-negative expression (P < .001 and P = .001; Fig 2A, B). Moreover, as CCR4 protein immu-noreactivity increased, the OS and DFS of patients with TSCC gradually decreased (Fig 2C, D).
    Table 2. EXPRESSION OF CCR4 AND ITS RELATION WITH CLINICAL FEATURES IN PATIENTS WITH TONGUE SQUAMOUS CELL CARCINOMA
    CCR4
    Gender
    Age
    Tobacco history
    Cell differentiation
    Tumor stage
    Abbreviations: , negative immunoreactivity; +, weak immu-noreactivity; ++, moderate immunoreactivity; +++, strong immunoreactivity; CCR4, chemokine (C-C motif) receptor-4.
    Wang et al. CCR4 Expression in pN0 Oral Tongue Cancer. J Oral Maxillofac Surg 2019. 
    UNIVARIATE AND MULTIVARIATE COX ANALYSES FOR PROGNOSES OF PATIENTS WITH TSCC
    To identify potential prognostic relevance, the uni-variate Cox model was applied to estimate the individ-ual clinical parameters for OS and DFS. Significant factors for OS were tumor stage (P < .001) and CCR4 expression (P = .001), and significant factors for DFS were tumor stage (P = .002) and CCR4 expression (P = .002). Then, these factors were included in the multivariate Cox model, which showed that tumor stage and CCR4 expression were independent prog-nostic factors for OS and DFS (Table 3).
    Discussion
    Local invasion and distant metastasis are the key fea-tures of primary tumors. Chemokine receptors are implicated in these processes of tumor progression.21 However, in the present study, the authors investi-gated the expression of CCR4 in patients with oral tongue cancer without lymphatic metastasis. To test the hypothesis that CCR4 is a novel prognostic biomarker for these patients, the authors detected its expression in surgically resected pN0 oral tongue can-cer specimens and investigated its correlation with clinicopathologic factors and the prognosis of patients. For the first time, the authors propose that CCR4 expression has potential as a new marker of a poor prognosis in patients with pN0 oral tongue cancer.