Detection of t(2;5) in anaplastic large cell lymphoma - Comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue

Detection of t(2;5) in anaplastic large cell lymphoma - Comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue
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DOI:
10.1097/00000478-199911000-00009
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发表时间:
1999-11-01
影响因子:
5.6
通讯作者:
Strickler, JG
Strickler, JG
中科院分区:
医学1区
文献类型:
--
作者:
Cataldo, KA;Jalal, SM;Strickler, JG

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间变性大细胞淋巴瘤(ALCL)与涉及间变性淋巴瘤激酶基因(ALK)和核磷蛋白基因(NPM)的t(2;5)(p23;q35)易位相关,这导致一种新型融合蛋白NPM-ALK(p80)的表达。临床病理学研究表明,与ALK表达缺失的ALCL相比,ALCL中的chat ALK表达与5年生存率改善相关。本研究采用石蜡包埋组织,比较间期荧光原位杂交(FISH)和逆转录-聚合酶链反应(RT-PCR)检测t(2;5)与免疫组化分析检测27例CD 30阳性ALCL患者ALK蛋白表达。27例患者中14例用ALK 1抗体检测ALK蛋白表达。这14个淋巴瘤中的13个中的肿瘤细胞与p80(NPM/ALK)抗体反应。使用双色ALK DNA探针的FISH与免疫组化结果100%相关:在所有14例与抗ALK 1反应的淋巴瘤中检测到涉及ALK基因的易位。对21例淋巴瘤进行RT-PCR,在5例淋巴瘤中检测到NPM-ALK mRNA,所有这些淋巴瘤均与抗ALK 1反应,并通过FISH显示ALK基因重排,显示ALK 1反应性的淋巴瘤发生在年轻患者人群中(中位年龄,19.5岁),与缺乏ALK 1反应性的淋巴瘤相比,(中位年龄68.0岁; 5年生存率35%; p = 0.008)。我们的结论是,免疫组化研究,使用抗体ALK 1,和FISH的ALK基因重排是同样有效的识别ALCL患者有良好的临床结果。
Anaplastic large cell lymphoma (ALCL) is associated with the t(2;5)(p23;q35) translocation involving the anaplastic lymphoma kinase gene (ALK) and the nucleophosmin gene (NPM), which result in expression of a novel fusion protein, NPM-ALK (p80). Clinicopathologic studies have shown chat ALK expression in ALCL is associated with improved 5-year survival rates when compared with ALCL lacking ALK expression. This study used paraffin-embedded tissue to compare interphase fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of t(2;5) with immunohistochemical analysis for the detection of ALK protein expression in 27 patients with CD30-positive ALCLs. ALK protein expression was detected with ALK1 antibody in 14 of the 27 patients. The neoplastic cells in 13 of these 14 lymphomas reacted with the p80(NPM/ALK) antibody. FISH, using a two-color ALK DNA probe, correlated 100% with the immunohistochemical results: a translocation involving the ALK gene was detected in all 14 lymphomas that: reacted with anti-ALK1. RT-PCR, performed on 21 lymphomas, detected NPM-ALK mRNA in five of the lymphomas, all of which reacted with anti-ALK1 and showed ALK gene rearrangement by FISH, Lymphomas showing ALK1 reactivity occurred in a younger patient population (median age, 19.5 years) and were associated with improved 5-year survival rates (84%), as compared with lymphomas lacking ALK1 reactivity (median age, 68.0 years; 5-year survival rate, 35%; p = 0.008). We conclude that immunohistochemical studies, using antibody ALK1, and FISH for ALK gene rearrangement are equally effective for identifying patients with ALCL who have a favorable clinical outcome.