Foss H D, Anagnostopoulos I, Araujo I, Assaf C, Demel G, Kummer J A, Hummel M, Stein H
Institute of Pathology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
Blood. 1996 Nov 15;88(10):4005-11.
To further specify the cellular origin and nature of anaplastic large-cell lymphoma (ALCL) and its relationship to other lymphoid neoplasms, particularly Hodgkin's disease (HD), we investigated the presence of cytotoxic molecules in a large well-characterized series of these tumors. For expression of the cytotoxic molecules perforin and granzyme B, in situ hybridization (ISH) and immunohistology were used, respectively. Overall, 23 of 25 ALCLs of T/null phenotype and five (three mixed cellularity and two nodular sclerosis) of 57 HD cases showed the presence of perforin transcripts and/or granzyme B molecules in neoplastic cells. Polymerase chain reaction (PCR) analysis of ALCLs showed that most (10 of 11) cases of null-cell ALCL (null-ALCL) contained a clonal rearrangement of T-cell receptor beta-chain genes, as did T-cell ALCL (T-ALCL; 9 of 10 cases). However, both cytotoxic molecules and clonally rearranged T-cell receptor beta-chain genes were absent in seven of seven and eight of nine cases of B-cell ALCL (B-ALCL), respectively. These data show that all or nearly all T-ALCLs, irrespective of the clinical subform or the lack of T-cell-associated molecules, are derived from activated cytotoxic T cells. The same appears to be true for the neoplastic cells of rare HD cases. These findings indicate that T-ALCLs are different from B-ALCLs and the majority of HD cases, and suggest that some HD cases, especially those with T-cell antigen-positive tumor cells, may be closely related to T-ALCL, at least in terms of cellular origin.
为了进一步明确间变性大细胞淋巴瘤（ALCL）的细胞起源、性质及其与其他淋巴样肿瘤尤其是霍奇金病（HD）的关系，我们在一系列特征明确的此类肿瘤中研究了细胞毒性分子的存在情况。对于细胞毒性分子穿孔素和颗粒酶B的表达，分别采用了原位杂交（ISH）和免疫组织学方法。总体而言，25例T/null表型的ALCL中有23例，57例HD中有5例（3例混合细胞型和2例结节硬化型）肿瘤细胞中存在穿孔素转录本和/或颗粒酶B分子。对ALCL进行聚合酶链反应（PCR）分析显示，大多数（11例中的10例）裸细胞ALCL（null-ALCL）病例含有T细胞受体β链基因的克隆重排，T细胞ALCL（T-ALCL；10例中的9例）也是如此。然而，7例B细胞ALCL（B-ALCL）中的7例和9例中的8例分别不存在细胞毒性分子和克隆重排的T细胞受体β链基因。这些数据表明，所有或几乎所有的T-ALCL，无论临床亚型如何或是否缺乏T细胞相关分子，均来源于活化的细胞毒性T细胞。罕见HD病例的肿瘤细胞似乎也是如此。这些发现表明T-ALCL与B-ALCL以及大多数HD病例不同，并提示一些HD病例，尤其是那些肿瘤细胞T细胞抗原阳性的病例，可能至少在细胞起源方面与T-ALCL密切相关。
