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弥漫性大B细胞淋巴瘤患者中Ki-67、CD10、BCL6、MUM1、c-MYC及EBV的表达与临床意义

Expression and Clinical Significance of Ki-67, CD10, BCL6, MUM1, c-MYC, and EBV in Diffuse Large B Cell Lymphoma Patients.

作者信息

Sadeghipour Alireza, Taha Seyed Reza, Shariat Zadeh Mahdieh, Kosari Farid, Babaheidarian Pegah, Fattahi Fahimeh, Abdi Navid, Tajik Fatemeh

机构信息

Department of Pathology, School of Medicine, Iran University of Medical Sciences.

Oncopathology Research Center, Iran University of Medical Sciences.

出版信息

Appl Immunohistochem Mol Morphol. 2024 Aug 1;32(7):309-321. doi: 10.1097/PAI.0000000000001208. Epub 2024 Jun 14.

Abstract

INTRODUCTION

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. Although studies regarding the association between the expression of Ki-67, CD10, BCL6, and MUM1 proteins, as well as c-MYC amplification and EBV status with clinicopathologic characteristics have rapidly progressed, their co-expression and prognostic role remain unsatisfactory. Therefore, this study aimed to investigate the association between the expression of all markers and clinicopathologic features and their prognostic value in DLBCL. Also, the co-expression of markers was investigated.

METHODS

The protein expression levels and prognostic significance of Ki-67, CD10, BCL6, and MUM1 were investigated with clinical follow-up in a total of 53 DLBCL specimens (including germinal center B [GCB] and activated B cell [ABC] subtypes) as well as adjacent normal samples using immunohistochemistry (IHC). Besides, the clinical significance and prognostic value of c-MYC and EBV status were also evaluated through chromogenic in situ hybridization (CISH), and their correlation with other markers was also assessed.

RESULTS

The results demonstrated a positive correlation between CD10 and BCL6 expression, with both markers being associated with the GCB subtype ( P< 0.001 and P =0.001, respectively). Besides, we observe a statistically significant association between MUM1 protein expression and clinicopathologic type ( P< 0.005) as well as a positive association between c-MYC and recurrence ( P =0.028). Our survival analysis showed that patients who had responded to R-CHOP treatment had better overall survival (OS) and progression-free survival (PFS) than those who did not.

CONCLUSION

Collectively, this study's results add these markers' value to the existing clinical understanding of DLBCL. However, further investigations are needed to explore markers' prognostic and biological roles in DLBCL patients.

摘要

引言

弥漫性大B细胞淋巴瘤(DLBCL)是成人非霍奇金淋巴瘤(NHL)最常见的类型。尽管关于Ki-67、CD10、BCL6和MUM1蛋白表达以及c-MYC扩增和EBV状态与临床病理特征之间关联的研究进展迅速,但其共表达情况和预后作用仍不尽人意。因此,本研究旨在探讨所有标志物的表达与临床病理特征之间的关联及其在DLBCL中的预后价值。此外,还研究了标志物的共表达情况。

方法

采用免疫组织化学(IHC)对53例DLBCL标本(包括生发中心B[GCB]和活化B细胞[ABC]亚型)以及相邻正常样本进行临床随访,研究Ki-67、CD10、BCL6和MUM1的蛋白表达水平及预后意义。此外,还通过显色原位杂交(CISH)评估c-MYC和EBV状态的临床意义和预后价值,并评估它们与其他标志物的相关性。

结果

结果显示CD10和BCL6表达呈正相关,这两种标志物均与GCB亚型相关(分别为P<0.001和P =0.001)。此外,我们观察到MUM1蛋白表达与临床病理类型之间存在统计学显著关联(P<0.005),c-MYC与复发之间存在正相关(P =0.028)。我们的生存分析表明,对R-CHOP治疗有反应的患者总生存期(OS)和无进展生存期(PFS)优于无反应者。

结论

总体而言,本研究结果为DLBCL的现有临床认识增添了这些标志物的价值。然而,需要进一步研究以探索这些标志物在DLBCL患者中的预后和生物学作用。

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