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间变大细胞淋巴瘤中 c-MYC 的异常表达和遗传改变。

Aberrant expression and genetic alteration of c-MYC in anaplastic large cell lymphoma.

机构信息

Department of Pathology, Fenyang College of Shanxi Medical University, Fenyang, China.

Department of Pathology, Shanxi Fenyang Hospital, Fenyang, China.

出版信息

J Cancer Res Clin Oncol. 2022 Jan;148(1):267-278. doi: 10.1007/s00432-021-03691-7. Epub 2021 Jun 16.

Abstract

PURPOSE

c-MYC plays an important role in regulating cellular growth and apoptosis, and it is aberrantly expressed in many human malignancies. Although c-MYC has been extensively investigated in Burkitt lymphoma and diffuse large B cell lymphoma, little has been reported in anaplastic large cell lymphoma (ALCL). The aim of this study was to investigate the expression and genetic alterations of c-MYC in primary systemic ALCL, characterize its clinicopathologic features and immunophenotypes, and discuss their implications in prognosis.

METHODS

Tissue microarrays using samples from 85 ALCL patients were used to evaluate expression of c-MYC and anaplastic lymphoma kinase (ALK). c-MYC and ALK genetic alterations were detected using fluorescence in situ hybridization. The Kaplan-Meier and multivariate Cox regression methods were used for survival analysis.

RESULTS

c-MYC was expressed in 24 of 85 samples (28.2%), and ALK was expressed in 54 (63.5%). c-MYC and ALK were co-expressed in 16 samples (18.8%). c-MYC expression and c-MYC and ALK co-expression increased with ALCL clinical stages and the International Prognostic Index (IPI) score (p < 0.05). Fifty of the samples (58.8%) had ALK rearrangement, and 18 (22.1%) had aneuploidy. c-MYC rearrangement was not detected, but aneuploidy was observed in 19 cases (22.4%). c-MYC aneuploidy was significantly different based on c-MYC expression and the IPI score (p < 0.05). c-MYC was a significant independent prognostic factor for progression-free survival and overall survival in patients with ALCL.

CONCLUSION

c-MYC protein expression and c-MYC aneuploidy could predict worse survival in patients with ALCL.

摘要

目的

c-MYC 在调节细胞生长和凋亡方面发挥着重要作用,在许多人类恶性肿瘤中异常表达。虽然 c-MYC 在伯基特淋巴瘤和弥漫性大 B 细胞淋巴瘤中得到了广泛研究,但在间变大细胞淋巴瘤(ALCL)中报道较少。本研究旨在探讨原发性系统性 ALCL 中 c-MYC 的表达和遗传改变,分析其临床病理特征和免疫表型,并探讨其对预后的影响。

方法

使用来自 85 例 ALCL 患者的组织微阵列评估 c-MYC 和间变性淋巴瘤激酶(ALK)的表达。使用荧光原位杂交检测 c-MYC 和 ALK 基因改变。采用 Kaplan-Meier 和多变量 Cox 回归方法进行生存分析。

结果

85 例样本中有 24 例(28.2%)表达 c-MYC,54 例(63.5%)表达 ALK。16 例样本(18.8%)同时表达 c-MYC 和 ALK。c-MYC 表达和 c-MYC 与 ALK 共表达随着 ALCL 临床分期和国际预后指数(IPI)评分的升高而增加(p<0.05)。50 例样本(58.8%)存在 ALK 重排,18 例(22.1%)存在非整倍体。未检测到 c-MYC 重排,但有 19 例(22.4%)存在非整倍体。c-MYC 非整倍体与 c-MYC 表达和 IPI 评分显著相关(p<0.05)。c-MYC 是 ALCL 患者无进展生存和总生存的独立预后因素。

结论

c-MYC 蛋白表达和 c-MYC 非整倍体可预测 ALCL 患者的生存较差。

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