【作者】 田荣华；

【导师】 应韶旭；

【作者基本信息】 苏州大学 ， 内科学， 2010， 硕士

【摘要】 研究背景与目的细胞过度增殖和凋亡受阻是肿瘤发生的关键,对DLBCL肿瘤细胞进行增殖和凋亡的研究,有助于揭示DLBCL发生发展的机制,了解肿瘤的生物学特性,为肿瘤的诊断、治疗和预后提供有价值的指标。Pim1在大多数肿瘤组织表达,具有抑制肿瘤细胞凋亡,促进肿瘤细胞增殖的功能。本研究针对国人NHL的流行病学特点,选取了我国患者好发的病理类型DLBCL,采用免疫组化技术,检测Pim1在DLBCL中的表达,探讨pim1与原发性结节性弥漫大B细胞淋巴瘤(DLBCL)预后的关系。材料和方法选取上海第六人民医院和南通大学附属医院2002年1月-2006年2月确诊的初发淋巴结起源的DLBCL 53例进行回顾性分析。应用兔抗人pim1多克隆抗体,采用免疫组化SP方法,根据抗原抗体反应的原理,检测53例DLBCL患者pim1的表达情况,结合临床及病理资料进行统计分析。结果1.Pim1在DLBCL患者中的表达情况:在53例DLBCL患者中,有24(45.2%)例pim1高表达,pim1高表达在年龄、性别、LDH水平、分期、B(有无)症状之间无明显差异(P>0.05),在IPI分组、生发中心表型、骨髓侵犯(有无)、化疗的完全缓解率相关存在差异(P<0.05)。2. Pim1的表达对患者化疗完全缓解率的影响:所有的53个患者全部接受了至少6-8个周期的CHOP方案的化疗,Pim1高表达的患者化疗完全缓解率是29.2%,pim1低表达患者的化疗完全缓解率是68.9%(p = 0.006)。在单因素logistic回归分析中显示pim1高表达患者的化疗完全缓解率的OR=0.263(95% CI, 0.084–0.825; P=0.022)。在包括pim1和IPI多因素logistic回归分析中,pim1高表达患者的化疗完全缓解率的OR=0.374(95% CI, 0.110–1.278; P=0.117) ,高-IPI组OR=0.235(95% CI, 0.069–0.801; P=0.021)。3. Pim1的表达对患者预后的影响:所有的53个患者全部接受了至少6-8个周期的CHOP方案的化疗,平均随访时间32个月(1-86个月),3年的总生存率是47.2%。Kaplan-Meier分析显示:Pim1高表达的患者比pim1低表达的患者3年总生存低(P<0.001)。单因素Cox回归分析表明,pim1高表达的RR=3.755(95% CI,1.684-8.375;P<0.001)。在包括pim1和IPI多因素Cox回归分析表明,pim1高表达的RR=2.756(95% CI,1.197-6.347;P=0.017);IPI的RR=2.947(95% CI,1.203-7.219;P=0.018)。结论1.Pim1的表达与性别、年龄、临床分期、B症状有无、LDH水平、≥2个结外受累部位无关,与IPI分组、生发中心表型、骨髓侵犯(有无)、化疗的完全缓解率相关。2.Pim1高表达的患者化疗后完全缓解率较pim1低表达患者低。3.Pim1高表达的患者3年总生存较pim1低表达的患者低。更多还原

【Abstract】 ObjectiveCell–immortalization and apoptosis-hindered are the tumorigenic foundation. The research about the proliferation and apoptosis of tumor cells is helpful to reveal the pathogenesis of tumor,understand the biology of tumor,provide valuable targets for the diagnosis, treatment and prognosis of the tumor. Pim1 is a proto-oncogene,expressed in most tumor tissues, while it may inhibit the apoptosis of tumor cells, promote the proliferation of tumor cells. According to the epidemiological characteristic of NHL in china, we have chosen DLBCL as objects of study, most common pathological type of NHL. We detected the expression of pim1 in DLBCL with immunohistochemistry. The purpose of this study was to investigate the prognostic significance of pim1 protein expression in primary nodal diffuse large B-cell lymphoma (DLBCL).MethodsFrom November 1993 to April 2001, 53 patients with histologically proven diagnoses of DLBCL were enrolled at Shanghai Sixth People’s Hospital and Hospital affiliated to Nantong University. According to the principle of antigen-antibody reaction, we detected the expression of pim1 in 53 cases with DLBCL with rabbit anti-human pim1 polyclonal antibody and the SP method of immunohistochemistry. Finally, we did statistical analysis combining with clinical and pathological data.Results1. Pim1 expression in DLBCL patients. In the DLBCL, there is 24 (45.2%) patients with high pim1 expression. There were no significant differences in terms of LDH, gender, age, B symptoms and stage according to the expression of pim1(P>0.05). However, there existed significant differences in terms of IPI, germinal center phenotype, complete remission of chemotherapy ,bone involvement(P<0.05). 2. Pim1 expression and response to chemotherapy in DLBCL patients. All patients were treated with 6-8 cycles of CHOP regimens at least. The complete remission rate after chemotherapy was 29.2% for patients with high pim1 expression and 68.9% for those with low pim1 expression (p = 0.006). In the univariate logistic analysis, the odds ratios for complete remission rate were 0.263 for high pim1 expression (95% CI, 0.084–0.825; P=0.022). In the multivariate logistic analysis included pim1 and IPI, these odds ratios were 0.374 for high pim1 expression (95% CI, 0.110–1.278; P=0.117) and 0.235 for high IPI (95% CI, 0.069–0.801; P=0.021).3. Prognostic significance of pim1 expression in DLBCL patients. All patients were treated with 6-8 cycles of CHOP regimens at least and followed up 32 months(range from 1 to 86 months). The 3-year overall survival rate of patients was 47.2%. Kaplan-Meier analysis revealed that the 3-year overall survival rate was higher in the pim1 low expression group than that in the pim1 high expression group. In the univariate Cox analysis, the relative risk for death was 3.7 for high pim1 expression. In the multivariate Cox analysis that included pim1 and IPI, the relative risk for death was 2.7 for high pim1 expression (95% CI, 1.2–6.3; P= 0.013) and 2.9 for high IPI (95% CI, 1.2–7.2; P = 0.012).Conclusion1. There were no significant differences in terms of LDH, gender, age, B symptoms and stage according to the expression of pim1. There existed significant differences, in terms of IPI, germinal center phenotype, complete remission of chemotherapy, bone involvement.2. In DLBCL, the complete remission rate after chemotherapy of patients with high pim1 expression is lower than low pim1 expression.3. In DLBCL, 3-year overall survival rate of patients was higher in the pim1 low expression group than that in the pim1 high expression group.更多还原