Immunohistochemical Approach to Genetic Subtyping of Anaplastic Large Cell Lymphoma.
Immunohistochemical Approach to Genetic Subtyping of Anaplastic Large Cell Lymphoma.
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免疫组织化学方法是对变类型大细胞淋巴瘤的遗传亚型。
DOI：
10.1097/pas.0000000000001941
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发表时间：
2022-11-01
影响因子：
5.6
通讯作者：
Dasari, Surendra
中科院分区：
文献类型：
--
作者：
Feldman, Andrew L.;Oishi, Naoki;Ketterling, Rhett P.;Ansell, Stephen M.;Shi, Min;Dasari, Surendra
间变性大细胞淋巴瘤（ALCL）可以根据ALK、TP 63和/或DUSP 22基因的重排（R）进行遗传分类。ALK-R定义了一种特定的实体，即ALK阳性ALCL，而DUSP 22-R和TP 63-R定义了具有不同临床病理学特征的ALK阴性ALCL亚组。ALK-R和TP 63-R产生可通过免疫组织化学检测的致癌融合蛋白。ALK免疫组织化学是ALK-R的极好替代物，p63 IHC筛查排除了三分之二ALCL中的TP 63-R。相反，DUSP 22-R不产生融合蛋白，其鉴定需要荧光原位杂交（FISH）。然而，DUSP 22-R ALCL具有特征性表型，包括细胞毒性标志物和磷酸化STAT 3 Y 705阴性。最近，我们还发现LEF 1转录因子在DUSP 22-R ALCL中过表达。在这里，我们试图验证这一发现，并使用LEF 1和TIA 1或磷酸化STAT 3 Y 705的免疫组织化学来检查预测DUSP 22-R的模型。我们在ALCL的原始发现队列（n=45）和独立验证队列（n=46）中评估了这3种标志物。DUSP 22-R和LEF 1表达之间的相关性在验证队列中强烈重复（P<0.0001）。此外，我们确定并验证了一种使用LEF 1和TIA 1免疫组织化学的策略，该策略在排除不确定病例后预测DUSP 22-R的阳性和阴性预测值均为100%，并且将消除65%的ALK阴性ALCL对FISH的需求。这种方法在相关疾病淋巴瘤样丘疹病中鉴定DUSP 22-R具有相似的结果。结合既往数据，这些发现支持使用ALK、LEF 1、TIA 1和p63进行ALCL基因亚型分型的4标记免疫组织化学算法。
Anaplastic large cell lymphoma (ALCL) can be classified genetically based on rearrangements (R) of the ALK, TP63, and/or DUSP22 genes. ALK-R defines a specific entity, ALK-positive ALCL, while DUSP22-R and TP63-R define subgroups of ALK-negative ALCLs with distinct clinicopathologic features. ALK-R and TP63-R produce oncogenic fusion proteins that can be detected by immunohistochemistry. ALK immunohistochemistry is an excellent surrogate for ALK-R and screening with p63 IHC excludes TP63-R in two-thirds of ALCLs. In contrast, DUSP22-R does not produce a fusion protein and its identification requires fluorescence in situ hybridization (FISH). However, DUSP22-R ALCL has a characteristic phenotype including negativity for cytotoxic markers and phospho-STAT3Y705. Recently, we also identified overexpression of the LEF1 transcription factor in DUSP22-R ALCL. Here, we sought to validate this finding and examine models for predicting DUSP22-R using immunohistochemistry for LEF1 and TIA1 or phospho-STAT3Y705. We evaluated these 3 markers in our original discovery cohort (n=45) and in an independent validation cohort (n=46) of ALCLs. The correlation between DUSP22-R and LEF1 expression replicated strongly in the validation cohort (P<0.0001). In addition, we identified and validated a strategy using LEF1 and TIA1 immunohistochemistry that predicted DUSP22-R with positive and negative predictive values of 100% after exclusion of indeterminate cases, and would eliminate the need for FISH in 65% of ALK-negative ALCLs. This approach had similar results in identifying DUSP22-R in the related condition, lymphomatoid papulosis. Together with previous data, these findings support a 4-marker immunohistochemistry algorithm using ALK, LEF1, TIA1, and p63 for genetic subtyping of ALCL.