Abstract 2429: Nestin expression in tumor cells is associated with BRCA1 positive genotype and a basal-like phenotype in breast cancer
Bibliographic record
Abstract
Abstract Background: The basal-like subtype of breast cancer is one of at least five molecular categories. These poor prognosis tumors are most often triple negative, i.e. negative for hormone receptors and HER2, and therefore lack targeted treatment options. There is at present no consensus on how to best define this subtype, and different surrogate immunohistochemistry based markers have been suggested. We here present data supporting nestin as a marker of the basal-like subtype. Originally reported in neuronal progenitor cells, nestin was later observed in the stem cell/progenitor compartment in a variety of tissues as well as in different cancer types, and suggested to be a cancer stem cell marker. In breast cancer, nestin has been reported in the basal-like and triple negative phenotypes. Here, we examined nestin expression in different breast cancer cohorts, including BRCA familial cancer, and breast cancer metastasis. Materials and methods: Immunohistochemical staining of nestin was done in four series of breast cancer, and a semi-quantitative measure of nestin positivity (staining index) was used for evaluation of expression. Series I include 190 breast cancer patients diagnosed during 1996-2001 in Hordaland, Norway. Series II comprise 192 breast cancer cases identified in Kampala, Uganda in 1990-2002. Series III includes 151 patients with breast cancer, 53 BRCA1 and 45 BRCA2 mutation carriers, identified during 1980-1995 in Montreal, Canada, and 51 BRCA negative patients from Norway. Series IV consists of 35 patients with tissue from the primary breast cancer and matched metastasis collected in 1996-2007. Finally, level 3 mRNA microarray data from TCGA (n = 520) and four open access breast cancer gene expression data sets (n = 1148) with information on molecular subtype were included. Results: The proportion of nestin positive breast tumors was 11%, 24% and 28% in Series I-III. Nestin expression was significantly associated with basal cell markers Cytokeratin 5/6 and P-cadherin (p-values <0.0005), five immunohistochemical profiles for the basal-like phenotype (Odds ratio, OR, range 10.9-27.5) and the triple negative phenotype (OR range 11.8-28.2). Further, patients with BRCA1 mutation more often had nestin positive tumors (OR 8.7, Series III). Higher nestin mRNA levels were seen in basal-like tumors, compared with the luminal-like and HER2-enriched subtypes. In Series IV, nestin expression in the primary tumor correlated with expression in the corresponding metastasis, with no statistically significant difference between the two groups (McNemar test, p = 1.0). Conclusion: We found nestin positivity in breast cancer cells to be significantly and strongly associated with the BRCA1 genotype, individual basal cell markers, and the basal-like and triple negative phenotypes. Citation Format: Kristi Krüger, Elisabeth Wik, Hawa Nalwoga, Monica Mannelqvist, Ingunn M. Stefansson, Jarle B. Arnes, Gøril Knutsvik, Turid Aas, William D. Foulkes, Lars A. Akslen. Nestin expression in tumor cells is associated with BRCA1 positive genotype and a basal-like phenotype in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2429. doi:10.1158/1538-7445.AM2015-2429
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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 | 0.000 | 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) | 0.001 | 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".