PARP1 expression in mantle cell lymphoma: the utility of PARP1 immunohistochemistry and its relationship with markers of DNA damage
Bibliographic record
Abstract
Mantle cell lymphoma (MCL) is an aggressive disease with poor overall survival, attributable in part to frequent defects of the DNA repair genes. In such malignancies, additional inhibition of the ubiquitous DNA damage repair protein, poly-ADP ribose polymerase-1 (PARP1) has shown enhanced cytotoxicity (so-called synthetic lethality). We studied PARP1 expression in a series of clinical cases of MCL, with the secondary aim to ascertain the relationship between PARP1 expression and DNA repair gene expression (namely ATM and p53) by immunohistochemical methods. We also examined the relationship between PARP1 expression and the well-established prognostic biomarker Ki-67, in addition to correlating PARP1 expression with the overall survival. From amongst our series of 79 unselected cases of MCL, we detected PARP1 expression in all but two cases with variable intensity. We also noted correlations between PARP1 expression and ATM and p53 expression. As described in previous studies, we identified a significant survival difference on the basis of Ki-67 and p53 expression. When digital H-score analysis of PARP1 expression was performed, there was a distinct survival advantage noted in patients with lower levels of expression. When our biomarker data were assessed by Cox regression, furthermore, the dominant effects of p53 and PARP1 expression were highlighted. Our data support the need for further research into the potential utility of PARP1 as a biomarker in MCL and for the potential direction of future PARP1 inhibitor-targeted therapy studies.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".