Amplification of the <i>TOP2A</i> gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples
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Bibliographic record
Abstract
Recent clinical trials have suggested that patients whose breast tumors overexpress HER2 may derive particular benefit from anthracycline-containing chemotherapy compared to that without anthracycline. It has been proposed that the HER2 gene amplification reported in these tumors might mask an underlying TOP2A gene amplification that occurs frequently and concurrently with HER2 amplification. Topoisomerase II alpha, encoded by TOP2A, is a direct molecular target of anthracycline drug action and is potentially useful as a predictive marker of response to anthracycline therapy for breast cancer. In this study, we examined whether TOP2A gene amplification is an appropriate marker for identifying breast tumors expressing high levels of topoisomerase II alpha. We determined topoisomerase II alpha protein expression by immunohistochemistry in 81 human breast tumors in relation to HER2 and TOP2A gene copy numbers analyzed by fluorescence in situ hybridization, histologic grade, cell proliferation fraction measured by MIB-1 expression, and HER2 protein expression determined by immunohistochemistry. The results showed no correlation between TOP2A gene copy number and topoisomerase II alpha protein expression levels in breast tumors, in contrast to the analogous situation for HER2 gene amplification and HER2 immunohistochemistry. Our results suggest that TOP2A gene amplification in breast tumors does not predict high expression of topoisomerase II alpha protein.
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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 it