Immunohistochemical detection of ZAP70 in chronic lymphocytic leukemia predicts immunoglobulin heavy chain gene mutation status and time to progression.
Immunohistochemical detection of ZAP70 in chronic lymphocytic leukemia predicts immunoglobulin heavy chain gene mutation status and time to progression.
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DOI：
10.1038/modpathol.2010.131
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发表时间：
2010-11
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通过流式细胞术测量的 Zeta 相关蛋白 70 (ZAP70) 表达已被提议作为慢性淋巴细胞白血病中免疫球蛋白重链可变区基因体细胞突变状态的替代标记。然而，在临床流式细胞术实验室中实施这种方法的尝试一直存在问题；许多市售抗体给出的结果不可靠。通过免疫组织化学评估慢性淋巴细胞白血病组织切片中的 ZAP70 蛋白表达是一种简单的替代方法，尽管缺乏定量和对结果的主观解释是潜在的缺陷。在本研究中，我们将通过免疫组织化学评估的 ZAP70 蛋白表达、通过半定量实时逆转录酶聚合酶链反应测定评估的 ZAP70 信使 RNA 转录本表达，与先前未经治疗的慢性淋巴细胞白血病患者的免疫球蛋白重链可变区基因的体细胞突变状态相关联。 ZAP70 蛋白和信使 RNA 转录本的表达密切相关 (p=8.238x10−12)。 ZAP70蛋白和信使RNA转录本的表达也与免疫球蛋白重链可变区基因的体细胞突变状态密切相关（分别为p=0.000071和p=0.00076）。此外，免疫组织化学检测的 ZAP70 阳性与进展至需要治疗的风险增加相关（免疫组织化学检测 ZAP70 阴性的 3 年风险为 83%，p=0.03）。这些结果表明，通过免疫组织化学评估的 ZAP70 表达是免疫球蛋白重链可变区基因体细胞突变状态的可靠替代标记，并预测进展时间。
Zeta-associated protein-70 (ZAP70) expression measured by flow cytometry has been proposed as a surrogate marker of the somatic mutation status of the immunoglobulin heavy chain variable region genes in chronic lymphocytic leukemia. However, attempts to implement this approach in clinical flow cytometry laboratories have been problematic; many commercially available antibodies give unreliable results. Assessment of ZAP70 protein expression by immunohistochemistry in chronic lymphocytic leukemia tissue sections is an easy, alternative approach, although lack of quantitation and subjective interpretation of results are potential pitfalls. In this study, we correlated ZAP70 protein expression, assessed by immunohistochemistry, with ZAP70 messenger RNA transcript expression, assessed by semi-quantitative real-time reverse transcriptase-polymerase chain reaction assay, with the somatic mutation status of the immunoglobulin heavy chain variable region genes in previously untreated patients with chronic lymphocytic leukemia. Expression of ZAP70 protein and messenger RNA transcripts correlated strongly (p=8.238x10−12). Expression of ZAP70 protein and messenger RNA transcripts also correlated strongly with the somatic mutation status of the immunoglobulin heavy chain variable region genes (p=0.000071 and p=0.00076, respectively). Further, ZAP70 positivity by immunohistochemistry was associated with an increased risk of progression to therapy requirement (3 year risk 83% vs. 31% for ZAP70 negative by immunohistochemistry, p=0.03). These results show that ZAP70 expression assessed by immunohistochemistry is a reliable surrogate marker of the somatic mutation status of the immunoglobulin heavy chain variable region genes, and predicts time to progression.
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