Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer
Bibliographic record
Abstract
// Xiaolan Feng 1,2,3 , Haocheng Li 3,4 , Elizabeth N. Kornaga 5,6 , Michelle Dean 5,6 , Susan P. Lees-Miller 7 , Karl Riabowol 7 , Anthony M. Magliocco 8 , Don Morris 3,6 , Peter H. Watson 9 , Emeka K. Enwere 5,6 , Gwyn Bebb 3,6 and Alexander Paterson 3 1 Department of Oncology, BC Cancer Agency-Vancouver Island Center, Victoria, British Columbia, Canada 2 Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada 3 Department of Oncology, Tom Baker Cancer Centre and University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada 4 Department of Community Health Science, TRW Building, University of Calgary, Calgary, Alberta, Canada 5 Functional Tissue Imaging Unit, Translational Research Laboratory, Tom Baker Cancer Centre, Calgary, Alberta, Canada 6 Translational Research Laboratory, Tom Baker Cancer Centre, Calgary, Alberta, Canada 7 Department of Biochemistry and Molecular Biology, Health Science Building, University of Calgary, Alberta, Canada 8 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA 9 Department of Pathology, BC Cancer Agency-Vancouver Island Center, Victoria, British Columbia, Canada Correspondence to: Xiaolan Feng, email: // Keywords : ATM, Ki67, early stage hormone receptor positive breast cancer, automated quantitative immunofluorescence analysis, disease specific overall survival Received : August 26, 2016 Accepted : October 05, 2016 Published : October 12, 2016 Abstract Introduction: This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. Methods: 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Results: Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up ( p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively ( p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status ( p = 0.02). Conclusions: These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.
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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".