Expression of T‐cell receptor signalling pathway components in extranodal <scp>NK</scp>/T‐cell lymphoma
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".