Wang C, Chen X, Chen X Y, You Z J
Department of Pathology, Fujian Provincial Hospital, Fujian Provincial; Clinical College of Fujian Medical University, Fuzhou 350001, China.
Zhonghua Bing Li Xue Za Zhi. 2021 Jun 8;50(6):598-603. doi: 10.3760/cma.j.cn112151-20201223-00953.
To investigate the genetic abnormality and protein expression of C-MYC and PD-L1 in the patients with ALK-negative anaplastic large cell lymphoma (ALKALCL), and to explore their roles in the pathogenesis of ALKALCL and their relationship with clinicopathological characteristics. Thirty-seven cases of ALKALCL 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. Among the 37 ALKALCL 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 (=0.990,=0.014). The protein expression of C-MYC and PD-L1 (versus negative) was associated with the clinical stage of ALKALCL, respectively. The international prognosis index (IPI) in high-risk group was higher than that in the low-risk group (<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 (<0.01 and <0.05), respectively. The expression of C-MYC and PD-L1 proteins are related to the clinical stage, IPI and overall survival rate of ALKALCL. Thus, it can be used to assess the disease's aggressiveness and to predict the prognosis of ALKALCL. The expression of PD-L1 in ALKALCL may be regulated by C-MYC, thus suggesting a possible design of combined C-MYC targeted therapy and immune checkpoint blocking for some ALKALCL patients.
探讨间变性淋巴瘤激酶阴性间变性大细胞淋巴瘤（ALK - ALCL）患者中C - MYC和程序性死亡受体配体1（PD - L1）的基因异常及蛋白表达情况，探讨其在ALK - ALCL发病机制中的作用及其与临床病理特征的关系。选取2003年1月至2017年1月在福建省立医院确诊的37例ALK - ALCL患者。采用荧光原位杂交（FISH）检测C - MYC和PD - L1的基因异常。采用免疫组织化学检测C - MYC和PD - L1蛋白的表达。分析C - MYC和PD - L1基因异常与蛋白表达之间的关系，以及它们与各种临床病理参数的相关性。在37例ALK - ALCL患者中，17例（45.9%）C - MYC蛋白阳性，14例（37.8%）PD - L1蛋白阳性。C - MYC蛋白与PD - L1蛋白之间存在显著相关性（=0.990，=0.014）。C - MYC和PD - L1蛋白表达（与阴性相比）分别与ALK - ALCL的临床分期相关。高危组的国际预后指数（IPI）高于低危组（<0.05）。FISH检测显示，37例中有9例（24.3%）存在C - MYC基因扩增，未发现任何病例有C - MYC基因易位。仅2例（5.4%）发现PD - L1基因扩增。C - MYC或PD - L1免疫组化阳性病例的3年总生存率分别显著低于C - MYC或PD - L1阴性病例（<0.01和<0.05）。C - MYC和PD - L1蛋白的表达与ALK - ALCL的临床分期、IPI及总生存率相关。因此，其可用于评估疾病的侵袭性并预测ALK - ALCL的预后。ALK - ALCL中PD - L1的表达可能受C - MYC调控，从而提示对于部分ALK - ALCL患者可能有联合C - MYC靶向治疗和免疫检查点阻断的设计方案。
