1Anhui Provincial Hospital, Cheeloo College of Medicine, Shan Dong University, Jinan, 250012, China; 2Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
2Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China; 3Intelligent Pathology Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
Acta Biochim Pol. 2022 Jul 25;69(3):559-565. doi: 10.18388/abp.2020_5833.
To investigate the relationship between expression of C-MYC protein and clinicopathologic characteristics in angioimmunoblastic T-cell lymphoma (AITL), then discuss the prognosis.
Patient samples were collected and made into tissue microarray for the same experimental condition. Pathomorphological features and immunohistochemistry of specific markers were used to determine the diagnosis of AITL. Epstein-Barr virus (EBV) infection was detected by EBV-encoded small RNA by in situ molecular hybridizations. B cells atypical hyperplasia was explored by the immunohistochemistry and gene rearrangement, C-MYC protein was expressed by the immunohistochemical staining and C-MYC gene abnormalities were detected by fluorescence in situ hybridization (FISH). 44 AITL patients were divided into two groups and the relation among C-MYC protein, EBV infection and B cells hyperplasia was observed. We followed up the overall survival rate (OS) and progression-free survival (PFS), and analyzed C-MYC protein, and the relationship between the prognosis of survival.
Among 44 AITL patients, 29 cases (65.9%) were C-MYC protein-positive, and 32 (32/44, 72.3%) were EBV-positive. The expression rate of C-MYC protein in the high-risk group ranked by international prognostic index (IPI) and stage III-IV were higher than that in the low-risk group and stage I-II (P<0.05). The expression rate of C-MYC protein was higher in B cells excessive proliferation group, including simple hyperplasia, atypical hyperplasia, monoclonal B cells hyperplasia, and the diffuse large B lymphoma than in the low-proliferation group (P<0.05). The expression rate of C-MYC protein in EBV-positive patients was indifferent compared with the negative group (P>0.05). C-MYC gene rearrangement was not found in any samples, while the multi-copies of the C-MYC gene were found in only one case. As followed, 5-year OS was significantly low, and there was no significant difference in OS between the C-MYC protein-positive and negative groups. PFS in the positive group was significantly lower than that of the negative group. The difference in response to treatment between the two groups was statistically significant (P<0.05).
We discussed the clinicopathologic characteristics and significance in AITLs, which predominantly express MYC-protein in <50% of cells, lacking C-MYC gene rearrangement. C-MYC protein-positive or negative expression was closely related to B cells excessive proliferation. C-MYC protein may be used as an indicator to judge the malignancy and to predict the prognosis of AITL.
探讨血管免疫母细胞性 T 细胞淋巴瘤（AITL）中 C-MYC 蛋白的表达与临床病理特征的关系，并探讨其预后。
收集患者样本制成组织微阵列，进行相同的实验条件下的检测。采用特定标志物的病理形态特征和免疫组织化学检测来确定 AITL 的诊断。通过原位分子杂交检测 EBV 编码的小 RNA 来检测 EBV 感染。通过免疫组织化学和基因重排探索 B 细胞非典型增生，通过免疫组织化学染色检测 C-MYC 蛋白的表达，通过荧光原位杂交（FISH）检测 C-MYC 基因异常。将 44 例 AITL 患者分为两组，观察 C-MYC 蛋白、EBV 感染与 B 细胞增生之间的关系。随访总生存率（OS）和无进展生存率（PFS），分析 C-MYC 蛋白与生存预后的关系。
在 44 例 AITL 患者中，29 例（65.9%）C-MYC 蛋白阳性，32 例（32/44，72.3%）EBV 阳性。国际预后指数（IPI）高危组和 III-IV 期患者的 C-MYC 蛋白高表达率高于低危组和 I-II 期（P<0.05）。在 B 细胞过度增殖组中，包括单纯增生、非典型增生、单克隆 B 细胞增生和弥漫性大 B 淋巴瘤，C-MYC 蛋白的表达率高于低增殖组（P<0.05）。与 EBV 阴性组相比，EBV 阳性患者的 C-MYC 蛋白表达率无差异（P>0.05）。未发现 C-MYC 基因重排，仅发现一例 C-MYC 基因多拷贝。随访 5 年，OS 明显降低，C-MYC 蛋白阳性组与阴性组之间的 OS 无显著差异。阳性组的 PFS 明显低于阴性组。两组的治疗反应差异有统计学意义（P<0.05）。
本文讨论了 AITL 的临床病理特征及意义，即<50%的细胞主要表达 MYC 蛋白，缺乏 C-MYC 基因重排。C-MYC 蛋白阳性或阴性表达与 B 细胞过度增殖密切相关。C-MYC 蛋白可作为判断 AITL 恶性程度和预测预后的指标。
