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弥漫性大B细胞淋巴瘤中缺氧标志物的初步研究

Preliminary study of hypoxia markers in diffuse large B-cell lymphoma.

作者信息

Pangarsa Eko A, Wuryantoro Probo, Naibaho Ridho M, Setiawan Budi, Santosa Damai, Istiadi Hermawan, Puspasari Dik, Suharti Catharina

机构信息

Division of Hematology/Medical Oncology, Department of Internal Medicine, Medical Faculty of Diponegoro University, Dr Kariadi Hospital, Semarang, Central Java 50244, Indonesia.

Department of Medicine, Palangkaraya Hospital, Palangkaraya, Central Kalimantan 73111, Indonesia.

出版信息

Mol Clin Oncol. 2022 Jul 28;17(3):140. doi: 10.3892/mco.2022.2573. eCollection 2022 Sep.

DOI:10.3892/mco.2022.2573
PMID:35949890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9353874/
Abstract

While the association of hypoxia has been established in various types of solid cancers, little is known about its presence and existence in diffuse large B-cell lymphoma (DLBCL). The purpose of the present study was to evaluate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in DLBCL and to analyze the association of these factors with several clinical and pathological characteristics. The immunohistochemical protein expression of HIF-1α and VEGF-A was investigated in 34 DLBCL tumor samples from January 2017 to December 2017 from the Department of Hematology/Medical Oncology and Anatomical Pathology at Dr Kariadi Hospital (Semarang, Indonesia). The present study revealed by using immunohistochemistry (IHC), that hypoxic markers were overexpressed (88.2% for both HIF-1α and VEGF-A) in the vast majority of patients with DLBCL. Only in 4 tumors, was HIF-1α expression normal, and interestingly VEGF-A was negative as well. There was a significant correlation in the intensity of staining of HIF-1α and VEGF-A using our custom scoring system in surgically resected tissues (r=0.475; P=0.005). Both HIF-1α and VEGF-A were also associated to serum LDH and tumor diameter. Collectively, HIF-1α and VEGF-A were predominantly expressed in the majority of DLBCL tumor cells. The findings of the present study indicate the existence of hypoxia in DLBCL tumors similar to numerous solid cancers, and thus warrants further investigation to clarify its role as a potential pathogenic or prognostic marker in this type of hematological cancer.

摘要

虽然缺氧与各种实体癌的关联已得到证实,但对于其在弥漫性大B细胞淋巴瘤(DLBCL)中的存在情况却知之甚少。本研究的目的是评估缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子A(VEGF-A)在DLBCL中的表达,并分析这些因子与若干临床和病理特征的关联。2017年1月至2017年12月期间,取自印度尼西亚三宝垄卡里阿迪医院血液学/医学肿瘤学和解剖病理学部门的34例DLBCL肿瘤样本,对HIF-1α和VEGF-A的免疫组化蛋白表达进行了研究。本研究通过免疫组化(IHC)发现,绝大多数DLBCL患者的缺氧标志物呈过表达(HIF-1α和VEGF-A均为88.2%)。仅在4个肿瘤中,HIF-1α表达正常,有趣的是VEGF-A也呈阴性。在手术切除组织中,使用我们的定制评分系统对HIF-1α和VEGF-A的染色强度存在显著相关性(r = 0.475;P = 0.005)。HIF-1α和VEGF-A均还与血清乳酸脱氢酶和肿瘤直径相关。总体而言,HIF-1α和VEGF-A在大多数DLBCL肿瘤细胞中主要表达。本研究结果表明,DLBCL肿瘤中存在缺氧情况,类似于众多实体癌,因此有必要进一步研究以阐明其作为这种血液系统癌症潜在致病或预后标志物的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ca/9353874/621204731fea/mco-17-03-02573-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ca/9353874/5af6c7b57c32/mco-17-03-02573-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ca/9353874/621204731fea/mco-17-03-02573-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ca/9353874/5af6c7b57c32/mco-17-03-02573-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ca/9353874/621204731fea/mco-17-03-02573-g01.jpg

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Blood. 2020 Jun 4;135(23):2041-2048. doi: 10.1182/blood.2019002729.
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