University Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Haematologica. 2013 Aug;98(8):1250-8. doi: 10.3324/haematol.2012.081935. Epub 2013 May 28.
Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30(+) peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30(+) and CD30(-); anaplastic large cell lymphomas, ALK(+) and ALK(-)), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30(-) tumors, CD30(+) peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK(-) anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30(-) peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30(+) subgroups. In conclusion, we show molecular and phenotypic features common to CD30(+) peripheral T-cell lymphomas, and significant differences between CD30(-) and CD30(+) peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups.
外周 T 细胞淋巴瘤，非特指型是一组具有模糊边界的侵袭性肿瘤。通过基因表达谱分析，我们之前报道了未特指的外周 T 细胞淋巴瘤的无监督聚类与 CD30 表达相关。在这项工作中，我们将外周 T 细胞淋巴瘤分子谱的分析扩展到典型的 CD30(+)外周 T 细胞淋巴瘤（间变大细胞淋巴瘤），并在蛋白质水平上验证了 mRNA 表达谱。重新分析了未特指的外周 T 细胞淋巴瘤和间变大细胞淋巴瘤的现有转录组数据集。选择了 21 种标记物用于 80 个外周 T 细胞淋巴瘤样本（非特指型、CD30(+)和 CD30(-)；间变大细胞淋巴瘤、ALK(+)和 ALK(-)）的免疫组织化学验证，并评估了亚组之间的差异。记录了临床随访情况。与 CD30(-)肿瘤相比，CD30(+)外周 T 细胞淋巴瘤，非特指型在 ALK(-)间变大细胞淋巴瘤相关基因中显著富集。通过免疫组织化学，CD30(+)外周 T 细胞淋巴瘤，非特指型与 CD30(-)样本有显著差异[T 细胞受体相关近端酪氨酸激酶（Lck、Fyn、Itk）和 T 细胞分化/激活相关蛋白（CD69、ICOS、CD52、NFATc2）表达下调；JunB 和 MUM1 上调]，同时与间变大细胞淋巴瘤重叠。CD30(-)外周 T 细胞淋巴瘤，非特指型的临床结局较 CD30(+)亚组差。总之，我们展示了 CD30(+)外周 T 细胞淋巴瘤的分子和表型特征，以及 CD30(-)和 CD30(+)外周 T 细胞淋巴瘤之间的显著差异，提示 CD30 表达可能划定了两个具有明显不同生物学特征的亚组。
