Objective To explore the expression and clinical significance of high mobility group box 1 (HMGB1) in stage ⅢB colon cancer. Methods Samples obtained from 72 patients with stage ⅢB colon cancer, who underwent surgery in Cancer Center of Sun Yat-sen University from Jun. 1999 to May 2002, were analyzed with single- and double-staining immunohistochemistry for the expression of HMGB1 and infiltration of inflammatory cells. Another fresh tissue samples obtained from 1O patients with stage Ⅲ colon cancer, who underwent surgery from Aug. to Oct. 2009, were analyzed with flow cytometry for the expression of CD3、CD45RO on the T cells, and the expressivities were then calculated. The expressive level and location of HMGB1, and the relationship of the expression to the infiltration of inflammatory cells and to 5-vear survival rate of patients were analvzed. The independent risk factors influencing the prognosis were screened out by Cox risk regression model with the 5-vear survival rate of 72 patients with stage ⅢB colon cancer as the dependent variable, and the clinical features, the expression level and location of HMGB1, and the infiltration density of CD3+ and CD45RO+ T cells as the independent variable. Results The expressions of CD3+ and CD15RO+T cells in different degree were found in the cytomembrane of interstitial tissues of stage Ⅲ colon cancer. It was revealed by flow cytometry that 72％ of the CD45RO+ T cells were also positive for CD3, and by immunohistochemical staining that the expression rate of HMGB1 was 90.3％ (65/72) in the tissues of stage Ⅲ colon cancer, of which 81.5％ (53/65) expressed on the nucleus alone and 18.5％ (12/65) on both nucleus and membrane, the infiltration density of CD45RO+ cells was higher in the former than in the latter. The infiltration density of CD45RO+ T cells was the independent risk factor for the surival of patients with stage Ⅲ colon cancer. Although no correlation was noted between HMGB1 expression, both in quantity and in location, and prognosis, the survival rate of patients with HMGB1 expressed on nucleus alone was higher than that of patients with HMGB1 expressed on both nucleus and membrane after a 24-month follow-up ( P＜0.001) . Conclusion The decrease of lymphocyte infiltration in the patients with HMGB1 expressed on both nucleus and membrane is companied with the decline of long-term survival rate of the patients with stage ⅢB colon cancer, implying the expressive style of HMGB1 may serve as one of the markers indicating the prognosis of patients with advanced local colon cancer.%目的 探讨ⅢB期结肠癌组织巾高迁移率族蛋白1(HMGB1)的表达与淋巴细胞浸润的关系及其临床意义.方法 收集1999年1月-2002年5月在中山大学肿瘤防治中心行手术切除的72例ⅢB期结肠癌标本,采用免疫组织化学染色及免疫双染技术分析HMGB1的表达和淋巴细胞浸润情况.收集2009年8-10月接受手术的10例Ⅲ期结肠癌患者的新鲜组织标本,采用流式细胞术分析组织中CD3+、CD45RO+T细胞的比例.分析HMGB1表达水平、表达部位与淋巴细胞浸润的关系及其与患者5年生存率的相关性.以72例ⅢB期结肠癌患者的5年生存率作为因变量,以各项临床特征、结肠癌组织HMGB1表达水平和表达部位、CD3+和CD45RO+T细胞的浸润密度等作为自变量,采用Cox比例风险回归模型筛选影响预后的独立危险因素.结果 ⅢB期结肠癌组织问质中可见不同程度CD3+、CD45RO+T细胞浸润,CD3和CD45RO均表达于细胞膜.流式细胞术分析可见,72%的CD45RO+细胞同时表达CD3.ⅢB期结肠癌组织HMGB1的表达率为90.3%(65/72),其中81.5%(53/65)为核型表达(仅表达在细胞核),18.5%(12/65)为核质共表达.核型HMGB1表达者的CD45RO+T细胞浸润密度高于核质共表达者.ⅢB期结肠癌组织中CD45RO+T细胞的浸润密度是影响患者生存的独立危险因素;HMGB1表达强度和表达部位与患者预后无关,但随访24个月以后,HMGB1核型表达者的5年生存率明显高于HMGB1核质共表达者(P＜0.001).结论 ⅢB期结肠癌患者出现HMGB1核质共表达时组织中淋巴细胞的浸润减少,患者长期生存率降低,提示HMGB1表达方式可作为反映局部晚期结肠癌患者预后的标志之一.
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