FET-Rearranged Myoepithelial Tumors Are Clinically Heterogeneous and Epigenetically Distinct from <i>PLAG1</i> -Rearranged Adnexal and Salivary Gland Myoepithelial Tumors
Bibliographic record
Abstract
PURPOSE: Fusion-positive myoepithelial tumors (MET) are clinicopathologically heterogeneous and variably termed mixed tumors and myoepithelial carcinomas. As FET-rearranged METs lack ductal/epithelial differentiation, we test whether FET-rearranged METs are epigenetically distinct from adnexal PLAG1-rearranged METs, which we hypothesize to be analogues of salivary gland METs. EXPERIMENTAL DESIGN: DNA methylation profiling from a multi-institutional cohort of 52 fusion-positive skin, soft-tissue, and bone MET cases was performed and compared with diverse tumor types, including salivary METs. The MET subgroups harbored EWSR1::KLF15, EWSR1/FUS::KLF17, EWSR1::PBX1, EWSR1::PBX3, EWSR1/FUS::POU5F1, SS18::POU5F1, EWSR1::ZNF444, and PLAG1 rearrangements. Pooled clinicopathologic and outcome analysis with new and published cases (total 185) was performed. RESULTS: The MET subgroups showed significant heterogeneity in age, site, and histology. Specifically, EWSR1::KLF15 METs affected predominantly young children (<5 years); EWSR1::PBX1/PBX3 METs were enriched in skin/bone; and EWSR1/FUS::POU5F1, SS18::POU5F1, and EWSR1::KLF15 METs tended to display malignant histology. Conversely, PLAG1-rearranged tumors were predominantly benign, arising in older adults and located in the skin. DNA methylation profiling revealed that FET-rearranged METs were epigenetically related to SS18::POU5F1 METs and FET::NFATC2 sarcomas but entirely distinct from PLAG1-rearranged adnexal and salivary METs. Histologic features were correlated with the degree of genome-wide copy-number variation. The median disease-specific survival was shortest in SS18::POU5F1 (31 months), EWSR1::PBX3 (38 months), and EWSR1::KLF15 (45 months) METs. On multivariate analysis, age <25 years was a significant predictor of worse progression-free survival. CONCLUSIONS: FET-rearranged METs are epigenetically unrelated to cutaneous and salivary gland METs, and their malignant counterparts are best classified as sarcomas rather than carcinomas.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".