Expression of T-cell receptor signalling pathway components in extranodal NK/T-cell lymphoma

Tomoko Miyata-Takata, Shih Sung Chuang, Katsuyoshi Takata, Tomohiro Toji, Yoshinobu Maeda, Yasuharu Sato, Tadashi Yoshino

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Aims: 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. Methods and results: 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). Conclusions: 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.

Original languageEnglish
Pages (from-to)1030-1038
Number of pages9
Issue number6
Publication statusPublished - Dec 2018


  • T-cell receptor pathway
  • extranodal NK/T-cell lymphoma
  • immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology


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