Amplification of the Prolactin Receptor Gene in Mammary Lobular Neoplasia.
Bibliographic record
Abstract
Abstract Background: Lobular carcinoma in situ (LCIS) has long been considered a marker of increased risk of cancer in both breasts. However, recent studies have shown that it can behave as a non-obligate precursor lesion as well. The biology and natural history of LCIS still remains ill defined in part because it is a challenging lesion to study as it usually does not have an identifiable gross appearance and is only recognized in fixed tissue specimens.Material and Methods: Using array comparative genomic hybridization (aCGH) we have analyzed regions of amplification found in LCIS and adjacent invasive lobular carcinoma (ILC) in a series of thirteen cases of archival patient samples from our institution. Degenerate oligonucleotide primed (DOP) PCR was performed for whole genome amplification of the extracted DNA from microdissected tissue samples prior to microarray analysis. Analysis of microarray data was performed using Significance Analysis of Microarrays (SAM). Of the ten most amplified genes in LCIS (highest SAM scores), one was selected for quantitative real time PCR (Q-PCR) validation due to the limited amount of material available from these cases. Q-PCR validation was performed on samples from 8 cases of LCIS and invasive lobular carcinoma and 12 archival cases of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) for comparison.Results: Amongst the 10 genes with the highest SAM scores, the prolactin receptor gene (PRLR) was selected for further Q-PCR validation in our limited samples. Amplification of PRLR was confirmed by Q-PCR in 4/8 (50%) of cases of LCIS and 4/8 (50%) cases of ILC, compared to 0/12 (0%) cases of DCIS and 3/12 (25%) cases of IDC. When LCIS and ILC were combined into one group, there was more amplification of the prolactin receptor gene when compared to the DCIS and IDC group (p= 0.01). The level of amplification between the two groups also differed in the range of copy number values, which was lower in the ductal group (0.78-1.58, n=24) compared to the lobular group (0.92-3.68, n=16) (p<0.05).Conclusion: We have identified the prolactin receptor as a potential molecular target in lobular neoplasia using array comparative genomic hybridization. In contrast, we have shown that the prolactin receptor may not be as important for the progression of ductal lesions. These results support the view that lobular and ductal carcinoma evolve along separate pathways. Validation of the expression of PRLR in a larger number of LCIS cases is warranted. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4151.
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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 | 0.000 |
| 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) | 0.001 | 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".