Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Pathology, Chi-Mei Medical Centre, Tainan, Taiwan.
Histopathology. 2018 Dec;73(6):1030-1038. doi: 10.1111/his.13728. Epub 2018 Oct 23.
Although the neoplastic cells of extranodal natural killer (NK)/T-cell lymphoma (ENKTL) usually do not express T-cell antigens, the T-cell receptor (TCR) gene might be rearranged and TCR protein expressed. The aim is to elucidate the expression of the downstream TCR pathway components and their importance in ENKTL.
We used formalin-fixed paraffin-embedded tissues from 91 ENKTL samples to immunohistochemically characterise the expression of TCR pathway components. The following proteins were variably expressed: ZAP70 (94%; 83/88), GRAP2/GADS (68%; 60/88), DOK2 (42%; 38/90), LCK (35%; 31/88), and ITK (10%; 9/90). When these tumours were classified as being of T lineage (16%), NK lineage (45%), or indeterminate lineage (38%), the GRAP2/GADS expression rate was higher in T lineage tumours (versus NK, P = 0.0073; versus indeterminate, P = 0.00082). GRAP2/GADS-positive NK lineage tumours more frequently expressed DOK2 (P = 0.0073), and were more often confined to the nasal areas (P = 0.014). Furthermore, when these tumours were immunophenotypically classified into a T signature (42%) or NK signature (58%), the expression rates of GRAP2/GADS and ITK were higher in T signature tumours (P = 0.00074 and P = 0.067, respectively), whereas that of LCK was higher in NK-signature tumours (P = 0.10).
Although some ENTKL cases were polyclonal for TCR rearrangement and others lacked TCR expression, we speculate that the TCR pathway might be functioning in ENKTLs. A T signature versus a NK signature might be better for delineating the physiology of ENKTL than cellular lineage. Furthermore, ITK may represent a potential therapeutic target for patients with ITK-expressing tumours.
尽管结外自然杀伤（NK）/T 细胞淋巴瘤（ENKTL）的肿瘤细胞通常不表达 T 细胞抗原，但 T 细胞受体（TCR）基因可能发生重排并表达 TCR 蛋白。本研究旨在阐明 TCR 下游途径成分的表达及其在 ENKTL 中的重要性。
我们使用 91 例 ENKTL 样本的福尔马林固定石蜡包埋组织，通过免疫组织化学方法对 TCR 途径成分的表达进行特征分析。以下蛋白表达存在差异：ZAP70（94%，83/88）、GRAP2/GADS（68%，60/88）、DOK2（42%，38/90）、LCK（35%，31/88）和 ITK（10%，9/90）。当这些肿瘤被分类为 T 细胞谱系（16%）、NK 细胞谱系（45%）或未确定谱系（38%）时，GRAP2/GADS 在 T 细胞谱系肿瘤中的表达率更高（与 NK 相比，P=0.0073；与未确定谱系相比，P=0.00082）。GRAP2/GADS 阳性 NK 细胞谱系肿瘤更常表达 DOK2（P=0.0073），且更常局限于鼻腔区域（P=0.014）。此外，当这些肿瘤通过免疫表型分类为 T 特征（42%）或 NK 特征（58%）时，GRAP2/GADS 和 ITK 在 T 特征肿瘤中的表达率更高（P=0.00074 和 P=0.067），而 LCK 在 NK 特征肿瘤中的表达率更高（P=0.10）。
尽管一些 ENTKL 病例 TCR 重排呈多克隆性，而另一些则缺乏 TCR 表达，但我们推测 TCR 途径可能在 ENKTL 中发挥作用。与细胞谱系相比，T 特征与 NK 特征可能更有助于描绘 ENKTL 的生理学。此外，ITK 可能代表表达 ITK 肿瘤患者的潜在治疗靶点。
