Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936
Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936
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DOI：
10.1038/sj.leu.2404482
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发表时间：
2007-02-01
期刊：
影响因子：
11.4
通讯作者：
Van Krieken, J. H. J. M.
中科院分区：
文献类型：
--
作者：
Langerak, A. W.;Molina, T. J.;Van Krieken, J. H. J. M.
淋巴细胞增生通常通过组织形态学和免疫组织化学诊断。虽然大多数是结论性的，但有时反应性病变和恶性淋巴瘤的鉴别诊断是困难的。在这种情况下，免疫球蛋白(Ig)/ t细胞受体（TCR）重排的分子克隆研究是有用的。在这里，我们使用标准化的BIOMED-2 Ig/TCR多重聚合酶链反应（PCR）异双工和GeneScan检测，解决了106个组织学上定义的反应性病变的克隆性评估问题。样本在全国范围内进行审查，除了10%的随机病例和克隆结果被选择用于额外的国际小组审查的病例。总共75%（79/106）只显示了Ig/TCR多克隆靶点（I型），而另外15%（16/106）可能是多克隆病例，在其他多克隆背景下具有弱Ig/TCR（寡克隆）克隆性（II型）。有趣的是，在10%（11/106）中观察到清晰的单克隆Ig/TCR产物（III/IV型），这促使进一步的病理检查。克隆性病例包括2例在全国综述中未发现的淋巴瘤，9例在进一步回顾中可解释为诊断困难病例或可能的淋巴瘤。我们的数据表明，BIOMED-2 Ig/TCR多重PCR检测非常有助于确认绝大多数反应性病变的多克隆特征。然而，在少数克隆检测应导致详细的病理检查，包括病理学家和分子生物学家的密切合作。
Lymphoproliferations are generally diagnosed via histomorphology and immunohistochemistry. Although mostly conclusive, occasionally the differential diagnosis between reactive lesions and malignant lymphomas is difficult. In such cases molecular clonality studies of immunoglobulin (Ig)/T-cell receptor (TCR) rearrangements can be useful. Here we address the issue of clonality assessment in 106 histologically defined reactive lesions, using the standardized BIOMED-2 Ig/TCR multiplex polymerase chain reaction (PCR) heteroduplex and GeneScan assays. Samples were reviewed nationally, except 10% random cases and cases with clonal results selected for additional international panel review. In total 75%(79/106) only showed polyclonal Ig/TCR targets ( type I), whereas another 15% (16/106) represent probably polyclonal cases, with weak Ig/TCR ( oligo) clonality in an otherwise polyclonal background ( type II). Interestingly, in 10% (11/106) clear monoclonal Ig/TCR products were observed ( types III/IV), which prompted further pathological review. Clonal cases included two missed lymphomas in national review and nine cases that could be explained as diagnostically difficult cases or probable lymphomas upon additional review. Our data show that the BIOMED-2 Ig/TCR multiplex PCR assays are very helpful in confirming the polyclonal character in the vast majority of reactive lesions. However, clonality detection in a minority should lead to detailed pathological review, including close interaction between pathologist and molecular biologist.