Prognostic impact of molecular genetic alterations in hepatoblastoma
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Bibliographic record
Abstract
BACKGROUND: During recent years, we identified characteristic genetic alterations in sporadic hepatoblastoma (HB). These include loss of heterozygosity (LOH) at the chromosomal region 11p15.5, LOH on chromosome arms 1p and 1q, activating mutations in exon 3 of the beta-catenin gene, as well as overexpression of the c-met oncogene, which encodes the hepatocyte growth factor receptor. We now wanted to evaluate the prognostic relevance of these abnormalities concerning the outcome in a large group of patients. PROCEDURE: All but 7 of 56 patients with HB were treated either with primary resection for small tumors, or neo-adjuvant chemotherapy with ifosfamide, cisplatin and doxorubicin (IPA) before delayed surgery in case of extended disease and additional adjuvant IPA therapy in all cases. Seven tumors were primarily resected and adjuvantly treated with different cytotoxic drugs. LOH 11p15.5, LOH 1p, and LOH 1q were detected in tumor tissue in comparison to normal liver and/or peripheral blood leukocytes by PCR based microsatellite analysis. Beta-catenin mutations were analysed with SSCP, deletion screening and direct sequencing. RT-PCR was used for identification of c-met mRNA overexpression. The results were correlated with the tumors' stage, histological type and epithelial differentiation, as well as with the patients' outcome. RESULTS: Overall disease-free survival after median follow-up of 5 years was 43/56 patients (77%). LOH 11p15.5 was found in 15/56, LOH1p in 11/53, LOH1q in 7/53 and beta-catenin mutations in 25/55 HB. 13/23 HB had a c-met overexpression. LOH 11p15.5 and LOH 1p were significantly more often found in embryonal HB, while there was no correlation of other genetic alterations with histological type or differentiation. Furthermore, statistical analysis revealed no correlation of any of these disorders with initial tumor stage, nor with the patients' outcome. CONCLUSION: None of the investigated molecular genetic alterations are suited to serve as a prognostic indicator in HB. Further investigations, especially genetic screening of tumor tissue may reveal prognostic markers for this neoplasm.
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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 | 0.000 | 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 it