Abstract 4187: Phospho-Akt status as a predictor of disease free interval in patients with muscle invasive transitional cell carcinoma of the bladder
Bibliographic record
Abstract
Abstract Background: Akt is an ubiquitous signaling molecule that is associated with a wide array of biological effects including cell growth and proliferation. The dysregulation of Akt has been associated with cancer cell transformation, invasion and metastasis. While the roles of mutations in FGFR3, p53 and Ras have been the focus of the majority of studies of Transitional cell carcinoma (TCC) of the bladder, recent evidence suggests a link between the Akt pathway and the progression of TCC. Mutations in Akt pathway members have been identified in subsets of bladder TCCs, and Akt activation in TCC cell lines confers resistance to chemotherapeutics and promotes invasion in vitro. This led us to hypothesize that activated Akt may be an important biomarker in the progression of muscle invasive TCC. Methods: Tissue was obtained from 67 patients who had undergone radical cystectomy procedures for treatment of muscle invasive TCC. Tissue sections were taken from paraffin embedded samples and subjected to immunohistochemical analysis with anti Akt antibody to detect the activated form of Akt. A database of patient demographics, disease, treatment and survival parameters was generated and used to correlate 4, 12, 24 and 36 month disease-free intervals (DFI). Results: 53 of the 67 patients had sufficient follow-up to allow for DFI analysis. Of these 53 patients, 48 stained positively for pAkt, while 5 stained negatively. None of the pAkt negative patients had recurrent disease, while the pAkt negative patients suffered cumulative recurrence in 10, 19, 24, and 25 of the 48 patients at 4, 12, 24 and 36 months respectively. Chi square analysis reveals statistically significant differences in recurrence rates between pAkt negative and negative patients at 24 (p=0.0235) and 36 months (p=0.016). Tumor stage and nodal status were also strong predictors of recurrence. Conclusions: pAkt negative patients were found to have a significantly better prognosis for TCC recurrence, which indicates that pAkt status could be useful in helping to determine the prognosis for patients with muscle invasive TCC. These results lead us to speculate that the use of a serine threonine kinase inhibitor may prove to be therapeutically beneficial for TCC patients undergoing concurrent chemotherapy for their disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4187. doi:10.1158/1538-7445.AM2011-4187
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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 | 0.001 |
| 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) | 0.002 | 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".