Persistence of AR signaling in small cell neuroendocrine prostate cancer (SCNC) and intermediate atypical carcinoma (IAC): Results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).
Bibliographic record
Abstract
5045 Background: De novo small cell neuroendocrine prostate carcinoma (SCNC) is an AR-null subtype observed in ~ 1% of patients (pts). We have observed a higher frequency of SCNC in castration-resistant metastatic biopsies (12%) as well as a morphologically distinct entity termed intermediate atypical carcinoma (IAC) (29%), both associated with shortened survival. We sought to determine whether treatment-emergent IAC and SCNC biopsies retained AR expression and signaling as compared with adenocarcinoma (adeno). Methods: Pts underwent a metastatic tumor biopsy of bone or soft tissue at one of 5 participating centers. Formalin fixed, paraffin-embedded tissue underwent pathologic review, fluorescence in situ hybridization (FISH) for assessment of AR amplification, and assessment of AR expression by immunohistochemistry (IHC). An AR transcriptional signature was applied to RNA sequencing (seq) data from frozen tissue. Results: Median serum PSA at the time of biopsy was 29 ng/mL (range 4-2250) for adeno, 123 (0.4-1600) for IAC, and 51 (0.6-930) for SCNC. AR amplification was seen in similar proportions of adeno (53%), IAC (58%), and SCNC tumors (53%) (p = ns). 2+/3+ nuclear AR expression by IHC was observed in 27/31 (87%), 21/24 (87%), and 7/9 (78%) of evaluable adenocarcinoma, IAC, and SCNC biopsies, respectively (p = ns). AR expression level by RNA-seq was likewise similar across histologies. AR transcriptional signature scores were similar between adeno and IAC histologies and lower in SCNC (p = 0.006), with considerable inter-patient variability noted in IAC. Conclusions: Contrary to the classical description of SCNC as an AR-null phenotype, the majority of metastatic SCNC and IAC biopsies were positive for AR amplification and expression. AR transcriptional activity was lower in SCNC, whereas IAC AR activity was comparable to adeno, potentially supporting IAC as a transitional state in which progressive loss of AR activity occurs. Longitudinal studies are ongoing to test this hypothesis. As novel therapeutic targets are identified in IAC and/or SCNC, continued co-targeting of the AR may be warranted. Clinical trial information: NCT02432001.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| 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) | 0.001 | 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".