Heterogeneity Between Ducts of the Same Nuclear Grade Involved by Duct Carcinoma In Situ (DCIS) of the Breast
Bibliographic record
Abstract
Naomi A. Miller1, Judith-Anne W. Chapman2, Jin Qian3, William A. Christens-Barry4, Yuejiao Fu5, Yan Yuan6, H. Lavina A. Lickley7 and David E. Axelrod81Department of Pathology, University Health Network, 200 Elizabeth St., Eaton 11-444, Toronto, Ontario, Canada. M5G 2C4. 2NCIC Clinical Trials Group, Queens University, 10 Stuart Street, Queens University, Kingston, Ontario, Canada. K7L 3N6. 3Math Elite Inc., 135 Arbour Crest Dr. NW, Calgary, AB, Canada, T3G 4L2. 4Equipoise Imaging LLC, 4009 St. Johns Lane, Ellicott City, MD, USA 21042. 5Department of Mathematics and Statistics, York University, 4700 Keele Street, Toronto, Ontario, Canada. M3J 1P3. 6Department of Population Health Research, Cancer Epidemiology, Prevention and Screening, Alberta Health Services, 1331-29th Street NW, Calgary, AB, Canada, T2N 4N2. 7Henrietta Banting Breast Centre, Women’s College Hospital, 76 Grenville Street, 7th floor, Toronto, Ontario, Canada. M5S 1B2. 8Department of Genetics and Cancer Institute of New Jersey, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082, USA. Abstract Purpose: Nuclear grade of breast DCIS is considered during patient management decision-making although it may have only a modest prognostic association with therapeutic outcome. We hypothesized that visual inspection may miss substantive differences in nuclei classified as having the same nuclear grade. To test this hypothesis, we measured subvisual nuclear features by quantitative image cytometry for nuclei with the same grade, and tested for statistical differences in these features.Experimental design and statistical analysis: Thirty-nine nuclear digital image features of about 100 nuclei were measured in digital images of H&E stained slides of 81 breast biopsy specimens. One field with at least 5 ducts was evaluated for each patient. We compared features of nuclei with the same grade in multiple ducts of the same patient with ANOVA (or Welch test), and compared features of nuclei with the same grade in two ducts of different patients using 2-sided t-tests (P ≤ 0.05). Also, we compared image features for nuclei in patients with single grade to those with the same grade in patients with multiple grades using t-tests.Results: Statistically significant differences were detected in nuclear features between ducts with the same nuclear grade, both in different ducts of the same patient, and between ducts in different patients with DCIS of more than one grade.Conclusion: Nuclei in ducts visually described as having the same nuclear grade had significantly different subvisual digital image features. These subvisual differences may be considered additional manifestations of heterogeneity over and above differences that can be observed microscopically. This heterogeneity may explain the inconsistency of nuclear grading as a prognostic factor.
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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 | 0.002 | 0.012 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".