摘要目的:探讨C-MYC和PD-L1基因和蛋白在间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤（ALK －ALCL）患者中的表达，探讨两者在ALK －ALCL发病机制中的作用以及与临床病理特征的关系。 方法:收集福建省立医院病理科2003年1月至2017年1月ALK －ALCL患者37例，应用荧光原位杂交（FISH）技术检测C-MYC和PD-L1基因异常情况；应用免疫组织化学方法检测C-MYC和PD-L1蛋白表达情况。统计分析C-MYC和PD-L1基因及蛋白异常的关系以及与各临床病理参数间的关系。 结果:37例ALK －ALCL肿瘤组织中，C-MYC蛋白阳性率为45.9%（17/37），PD-L1蛋白表达阳性率是37.8%（14/37），C-MYC和PD-L1蛋白表达之间存在显著相关性（ r=0.990， P=0.014）。C-MYC和PD-L1蛋白表达率均随ALK －ALCL临床分期的增加而升高，且在国际预后指数（IPI）高危组中表达率高于低危组（ P<0.05）。FISH检测结果：37例ALK －ALC肿瘤组织中，检测到C-MYC基因多拷贝9例（24.3%），所有病例均未检测到C-MYC基因断裂；检测到PD-L1基因扩增2例（5.4%）。37例ALK －ALCL患者中，C-MYC蛋白阳性表达组3年总生存率明显低于阴性表达组，差异具有统计学意义（ P<0.01）；PD-L1蛋白阳性表达组3年总生存率明显低于阴性表达组，差异具有统计学意义（ P<0.05）。 结论:C-MYC蛋白和PD-L1蛋白表达与ALK －ALCL临床分期、国际预后指数以及总生存率相关，可作为判断ALK －ALCL恶性程度和预测预后的指标；ALK －ALCL中PD-L1的表达可能受C-MYC基因的调控，可能为设计针对部分ALK －ALCL患者的靶向治疗和免疫检查点阻断的组合治疗提供了生物学基础。

abstractsObjective:To investigate the genetic abnormality and protein expression of C-MYC and PD-L1 in the patients with ALK-negative anaplastic large cell lymphoma (ALK －ALCL), and to explore their roles in the pathogenesis of ALK －ALCL and their relationship with clinicopathological characteristics. Methods:Thirty-seven cases of ALK －ALCL diagnosed at Fujian Provincial Hospital from January 2003 to January 2017 were selected. Fluorescence in situ hybridization (FISH) was used to detect the genetic abnormality of C-MYC and PD-L1. The expression of C-MYC and PD-L1 proteins was detected by immunohistochemistry. The relationship between C-MYC and PD-L1 genes′ abnormalities and protein expression was analyzed, as well as their associations with various clinicopathological parameters. Results:Among the 37 ALK －ALCL patients, 17 (45.9%) were positive for C-MYC protein, and 14 (37.8%) were positive for PD-L1 protein. There was a significant correlation between C-MYC protein and PD-L1 protein ( r=0.990, P=0.014). The protein expression of C-MYC and PD-L1 (versus negative) was associated with the clinical stage of ALK －ALCL, respectively. The international prognosis index (IPI) in high-risk group was higher than that in the low-risk group ( P<0.05). FISH test showed that 9 (24.3%) of the 37 cases had amplification of C-MYC gene, and no translocation of C-MYC gene was found in any of the cases. Amplification of PD-L1 gene was found in only 2 cases (5.4%). The 3-year overall survival rate of the C-MYC or PD-L1 immunohistochemistry-positive cases was significantly lower than those of the C-MYC or PD-L1 negative cases ( P<0.01 and P<0.05), respectively. Conclusion:The expression of C-MYC and PD-L1 proteins are related to the clinical stage, IPI and overall survival rate of ALK －ALCL. Thus, it can be used to assess the disease′s aggressiveness and to predict the prognosis of ALK －ALCL. The expression of PD-L1 in ALK －ALCL may be regulated by C-MYC, thus suggesting a possible design of combined C-MYC targeted therapy and immune checkpoint blocking for some ALK －ALCL patients.