Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor
Bibliographic record
Abstract
AIMS: Recent evidence indicates that weakly positive immunohistochemical staining of oestrogen receptor (ER) is not associated reliably with a luminal subtype, with the majority reclassified as basal-like by gene expression profile. In this study we assessed the capacity of recently identified immunohistochemical markers of basal-like subtype not dependent upon ER status - positive expression of nestin or loss of inositol polyphosphate-4-phosphatase (INPP4b) - to discriminate intrinsic subtypes, focusing on clinically problematic cases with weak ER positivity. METHODS AND RESULTS: Formalin-fixed paraffin-embedded blocks, enriched for large proportions of ER-negative and ER weakly positive breast cancers, were selected from two previous studies conducted in the period 2008-13 and used for (i) RNA extraction for 50-gene subtype predictor (PAM50) intrinsic subtyping and (ii) tissue microarray construction for immunohistochemical assessment of nestin and INPP4b. Fifty-eight cases were weakly positive for ER (Allred 3-5), among which 28 (48%) were assigned as basal-like by PAM50 gene expression. In these 58 cases, the nestin/INPP4b panel identified 23 basal-like cases with a positive predictive value of 87% [95% confidence interval (CI) 78-95%] and excluded luminal subtype with a negative predictive value of 95% (95% CI 88-100%). Weakly positive ER patients assigned as basal-like by nestin/INPP4b definition demonstrated a median survival time of 45.8 months, significantly lower than 65 months among other ER weakly positive cases (P = 0.012). CONCLUSIONS: Immunohistochemical assessment of nestin and INPP4b provides an accurate, accessible and inexpensive tool to identify basal-like breast cancer subtype in the clinically problematic setting of weak ER positivity. This panel identifies poor prognosis patients who might need strong considerations for non-endocrine-based therapies.
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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) | 0.000 | 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".