Investigations into molecular alterations present in ductal carcinoma in situ of the breast using a murine mammary tumor model
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 46, 2005 1073 Ductal carcinoma in situ (DCIS), an alleged precursor of invasive breast cancer, is characterized by neoplastic epithelial cells growing within mammary ducts. One of the most critical stages in the development of breast cancer is the progression from DCIS to invasive carcinoma, when the basement membrane of the duct is breached and tumour cells spill out into the surrounding stroma. Clinical prognostication for DCIS is challenging, as the likelihood of progression to invasion by low-grade DCIS and the potential for low-grade lesions to evolve to high-grade both remain unclear. The small size of lesions, coupled with variations in time to invasion and rates of post-treatment recurrence, have complicated the study of DCIS in humans. The MMTV- neu 202Mul mouse model has been reported to develop DCIS-like lesions in the mammary fat pads. When a tumour is detected by manual palpation, the animal is sacrificed and the mammary fat pads are removed. Tissues are prepared as both snap-frozen and formalin-fixed paraffin-embedded (FFPE) blocks, sectioned, stained with haematoxylin and eosin, and assessed for quality. Immunohistochemical staining for smooth muscle actin (SMA) reveals the myoepithelial cells which are wrapped around the basement membrane of the ducts. Assessing the continuity of the myoepithelial cell line permits classification of tumours as either DCIS, invasive, or focally invasive. FFPE sections of DCIS and fully invasive samples are then microdissected. DNA is extracted and examined using array comparative genomic hybridization. Analysis has revealed differing patterns of genomic amplification and deletion between the two tumour types. Copy numbers of Gas6 and Psmb3 have been found amplified in invasive carcinoma. To assess gene expression levels, RNA is extracted from frozen DCIS and fully invasive tumours and analysed via expression microarray. Array profiling has revealed altered expression of genes including Tsga2 , Grb7 , Arl1 , and Phka2 . Preliminary data indicate that these genes have higher expression in DCIS. Gene copy number and gene expression differentials will be further analyzed using quantitative polymerase chain reaction (Q-PCR). Immunohistochemistry is being employed to develop a profile of the tumour types. Targets including Ki67, Laminin, Activated Caspase 3, E-Cadherin, and CD31 have been assessed. These data indicate differences in the expression of certain markers between tumour types. In comparison to DCIS tumours, invasive tumours have shown an increase in expression of Ki67 but a decreased expression of Activated Caspase 3. Additional immunohistochemistry is ongoing, as is collection and analysis of microarray data. Through comparison of data from mouse and human cases, we plan to identify a subset of genes which could be used as prognostic markers and/or therapeutic targets to improve clinical management of human DCIS cases.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".