Prognostic value of p53 mutations in oesophageal adenocarcinoma: final results of a 15-year prospective study
Bibliographic record
Abstract
OBJECTIVE: This study evaluates the clinical significance of p53 mutations in oesophageal adenocarcinoma (EADC). METHODS: Between February 1991 and February 2006, 142 consecutive patients with EADC underwent potentially curative oesophageal resection. No patient received induction therapy. Strict clinicopathologic criteria were used to define primary EADC (Type I), excluding gastric cardia adenocarcinoma (Type II). Genomic DNA was extracted from oesophageal tumours, each with matched histologically normal oesophageal epithelium (internal control) from the resection margin. Polymerase chain reaction was used to amplify p53 exons 4-10, and mutations were characterised by direct DNA sequencing. The p53 mutations were correlated with clinicopathologic findings, p53 protein expression determined using immunohistochemistry, and outcome using Kaplan-Meier and Cox proportional hazards models. RESULTS: For all patients, 5-year overall survival (OS) was 26.9%. Conventional predictors of reduced OS included advanced pathological tumour-node-metastasis (pTNM) stage (P<0.0001) and number of involved lymph nodes (0, 1-3, >3; P<0.0001). No p53 mutations were found in normal oesophageal epithelia. A total of 47% of tumours (67/142) had p53 mutations, predominantly G:C to A:T transitions at CpG dinucleotides (36/67). The p53 mutations were associated with p53 protein overexpression (P<0.0001) and poor tumour differentiation (P=0.037). Patients whose tumours had p53 mutations had significantly reduced 5-year OS (hazard ratio (HR): 1.54; 95% confidence interval (CI): 1.03-2.3; P=0.03). CONCLUSIONS: Patterns of p53 mutations in EADC suggest endogenous molecular mechanisms. The p53 mutations are a predictor of significantly reduced postoperative survival following surgical resection of EADC, and would appear to be a clinically useful molecular prognostic biomarker.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".