生发中心相关标志物GCET1、HGAL和LMO2在血液淋巴系统肿瘤中的诊断效用

Diagnostic Utility of the Germinal Center-associated Markers GCET1, HGAL, and LMO2 in Hematolymphoid Neoplasms.

作者信息

Menter Thomas, Gasser Anjes, Juskevicius Darius, Dirnhofer Stephan, Tzankov Alexandar

机构信息

Institute of Pathology, University Hospital Basel, Basel, Switzerland.

出版信息

Appl Immunohistochem Mol Morphol. 2015 Aug;23(7):491-8. doi: 10.1097/PAI.0000000000000107.

Abstract

Implementation of new phenotypic markers in routine diagnostics of hematolymphoid neoplasms is a challenging task with a plethora of potentially relevant proteins. We investigated 3 recently discovered proteins expressed in the germinal centers of lymph nodes (LMO2, GCET1, and HGAL) in a compilation of leukemia, lymphoma, and thymic tumor entities. Altogether, 1590 cases (1519 on tissue microarrays, 71 on conventional slides) were included. Expressions of LMO2, GCET1, and HGAL were investigated by immunohistochemistry, evaluated for their differential diagnostic relevance, and correlated with the clinical outcome of patients. In Hodgkin lymphoma (HL), the expression of LMO2, GCET1, and HGAL could be largely seen in tumor cells of nodular lymphocyte predominant HL (NLPHL) but only occasionally in classic HL. The majority of B-cell lymphoma cases was positive for LMO2 [except for Burkitt lymphoma (BL)] and HGAL with weaker to moderate staining intensity, compared with the intensely staining follicular lymphomas (FL). Except for FL (60% of cases) and diffuse large B-cell lymphomas (DLBCL, 36% of cases), all other B-cell lymphomas expressed little or no GCET1. In thymomas, the non-neoplastic immature T-cells were LMO2-negative, whereas the neoplastic lymphoblasts were LMO2-positive in more than half of the lymphoblastic lymphomas (LBL). Our findings provide new potential assistance in the differential diagnosis of FL to marginal zone lymphoma, classic HL to NLPHL and primary mediastinal B-cell lymphoma, DLBCL to BL, and thymoma to LBL. Finally, HGAL proved to be a prognostic marker for classic HL regarding the background population and in DLBCL regarding the tumor cells.

摘要

在血液淋巴系统肿瘤的常规诊断中应用新的表型标志物是一项具有挑战性的任务,因为存在大量潜在相关蛋白。我们在一组白血病、淋巴瘤和胸腺肿瘤实体中研究了最近发现的3种在淋巴结生发中心表达的蛋白(LMO2、GCET1和HGAL)。总共纳入了1590例病例(1519例在组织芯片上,71例在传统载玻片上)。通过免疫组织化学研究LMO2、GCET1和HGAL的表达,评估其鉴别诊断相关性,并与患者的临床结局相关联。在霍奇金淋巴瘤(HL)中,LMO2、GCET1和HGAL的表达主要见于结节性淋巴细胞为主型HL(NLPHL)的肿瘤细胞,而在经典HL中仅偶尔可见。大多数B细胞淋巴瘤病例LMO2呈阳性[除伯基特淋巴瘤(BL)外],HGAL呈阳性,染色强度弱至中度,而滤泡性淋巴瘤(FL)染色强烈。除FL(60%的病例)和弥漫性大B细胞淋巴瘤(DLBCL,36%的病例)外,所有其他B细胞淋巴瘤几乎不表达或不表达GCET1。在胸腺瘤中,非肿瘤性未成熟T细胞LMO2阴性,而在超过一半的淋巴母细胞淋巴瘤(LBL)中,肿瘤性淋巴母细胞LMO2阳性。我们的研究结果为FL与边缘区淋巴瘤、经典HL与NLPHL以及原发性纵隔B细胞淋巴瘤、DLBCL与BL、胸腺瘤与LBL的鉴别诊断提供了新的潜在帮助。最后,对于经典HL的背景人群和DLBCL的肿瘤细胞,HGAL被证明是一种预后标志物。

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