Abstract P4-09-07: ING1 Expression Measured by AQUA can be an Independent Prognostic Marker in Breast Cancer
Bibliographic record
Abstract
Abstract Background: Breast cancer accounts for around 45,000 cancer related deaths in North America per year. The high incidence of breast cancer observed in this region is most likely due to the availability of various screening programs used to detect breast cancer, which otherwise may never get diagnosed. There is an inverse relation between the cost of treatment and patient survival as the breast cancer progresses to higher grades. Therefore, screening and diagnosing breast cancers at earlier stages is needed which can improve patient survival. The INhibitor of Growth (ING) family of tumour suppressor proteins are implicated in diverse cellular processes including chromatin remodelling and apoptosis. ING proteins are stoichiometric members of histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes. Their expression is downregulated in several cancers, including breast carcinoma. Alternatively, ING function may be compromised by mislocalization to the cytoplasm. However, the association of expression of ING proteins and cancer specific survival has not been studied yet. In this study, we aimed to evaluate the prognostic significance of ING1 in breast cancer. Patients and Methods: This study included 443 Breast Cancer patients diagnosed in Calgary, Canada from 1985–2000. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin-embedded tumour tissue. ING1 protein expression was quantified using fluorescent immunohistochemistry and automated quantitative analysis (AQUA) in normal breast epithelial cells and breast cancer samples. 5 year progression free survival (PFS) was analyzed using Kaplan-Meier plots and Cox proportional hazard modelling. Results: In our study, we found that ING1 expression is significantly downregulated in the breast cancer patient samples relative to normal breast epithelia. High or low ING1 cytoplasmic/nuclear (C/N) ratio results in poor 5 year PFS. Also, the low tumor/stromal (t/s) ratio of ING1 results in poor prognosis. In univariate analysis, t/s ING1 expression showed a negative correlation with tumor stage [p = 0.008]; tumor grade [p = 0.000]; nodal status [p = 0.000] and 5 year PFS [p = 0.004]. However, no correlation was observed with ER, PR or HER2 status. In multivariate analysis, t/s ING1 proved to be an independent and better prognostic marker [HR 0.582, p = 0.037] than HER2 [HR 2.230, p = 0.057]; Age at diagnosis [HR 2.010, p = 0.205] and tumor size [HR 1.471, p = 0.189]. Discussion and Conclusions: This is the first study to evaluate ING1 expression in breast cancer using the AQUA technique. ING1 expression high or low in the C/N ratio might disrupt the stoichiometry of chromatin-modifying complexes and hamper ING1s extra nuclear functions, leading to poor survival. The significantly improved survival observed in patients with high t/s ING1 expression further strengthens the role of ING1 as a tumor suppressor. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-09-07.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.004 | 0.001 |
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".