Chiang A K, Chan A C, Srivastava G, Ho F C
Department of Pathology, The University of Hong Kong, Hong Kong.
Int J Cancer. 1997 Nov 4;73(3):332-8. doi: 10.1002/(sici)1097-0215(19971104)73:3<332::aid-ijc5>3.0.co;2-0.
The cellular nature of nasal T/natural killer (NK)-cell lymphomas (NLs) remains controversial. It is still debatable whether these represent T-cell lymphomas with extensive loss of surface antigens or are, in fact, true NK-cell lymphomas. They are associated closely with Epstein-Barr virus (EBV), to the extent that EBV-encoded small non-polyadenylated RNAs (EBER) expression can be used as a marker for the neoplastic cells. The cell lineage of this group of lymphomas was examined further by correlating immunophenotype, genotype and EBV status with the expression of cytotoxic granule-associated proteins, perforin and T-cell intracellular antigen-1 (TIA-1) in 13 cases of NL. Combined immunophenotypic and gene rearrangement analyses demonstrated that NLs can be identified clearly as either NK-cell or T-cell tumours. Nasal NK-cell lymphomas lacked clonal rearrangement of both T-cell receptor (TCR) gamma and immunogloulin heavy chain (IgH) genes and were either CD3(Leu4)-CD56+ (8 cases) or CD3(Leu4)+CD56+ (2 cases), whereas nasal T-cell lymphomas had rearranged TCRgamma and germ-line IgH genes and were either CD3(Leu4)+CD56+ (2 cases) or CD3(Leu4)+CD56- (1 case). Immunohistochemical (IH) studies showed that both perforin and TIA-1 were expressed universally in NL, irrespective of NK- or T-cell lineage. Dual labelling of TIA-1 by IH and EBER by in situ hybridisation demonstrated that the granule proteins were expressed predominantly by the EBER+ tumour cells. Our results indicate that NLs are derived from EBV-infected cytotoxic lymphocytes of both NK- and T-cell lineage. We postulate that cytotoxic lymphocytes generated during the cellular immune response to EBV infection or re-activation at the nasal region themselves may become targets for EBV infection and subsequent transformation.
鼻腔T/自然杀伤（NK）细胞淋巴瘤（NLs）的细胞本质仍存在争议。这些肿瘤究竟是表面抗原广泛缺失的T细胞淋巴瘤，还是实际上的真正NK细胞淋巴瘤，仍有争议。它们与爱泼斯坦 - 巴尔病毒（EBV）密切相关，以至于EBV编码的小非多聚腺苷酸化RNA（EBER）表达可作为肿瘤细胞的标志物。通过将免疫表型、基因型和EBV状态与13例NL中细胞毒性颗粒相关蛋白、穿孔素和T细胞胞内抗原-1（TIA-1）的表达进行关联，对这组淋巴瘤的细胞谱系进行了进一步研究。联合免疫表型和基因重排分析表明，NLs可明确鉴定为NK细胞或T细胞肿瘤。鼻腔NK细胞淋巴瘤缺乏T细胞受体（TCR）γ和免疫球蛋白重链（IgH）基因的克隆重排，且要么为CD3（Leu4）-CD56 +（8例），要么为CD3（Leu4）+CD56 +（2例），而鼻腔T细胞淋巴瘤具有重排的TCRγ和种系IgH基因，且要么为CD3（Leu4）+CD56 +（2例），要么为CD3（Leu4）+CD56 -（1例）。免疫组织化学（IH）研究表明，无论NK或T细胞谱系如何，穿孔素和TIA-1在NL中均普遍表达。通过IH对TIA-1和原位杂交对EBER进行双重标记表明，颗粒蛋白主要由EBER +肿瘤细胞表达。我们的结果表明，NLs源自NK和T细胞谱系的EBV感染的细胞毒性淋巴细胞。我们推测，在对EBV感染或鼻腔区域再激活的细胞免疫反应过程中产生的细胞毒性淋巴细胞本身可能成为EBV感染及随后转化的靶标。
