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| Home > Publications database > Clinically Tractable Outcome Prediction of non-WNT/non-SHH Medulloblastoma Based on TPD52 Immunohistochemistry in a Multicohort Study. |
| Home > Publications database > Clinically Tractable Outcome Prediction of non-WNT/non-SHH Medulloblastoma Based on TPD52 Immunohistochemistry in a Multicohort Study. |
| Journal Article | DKFZ-2021-02359 |
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2022
AACR
Philadelphia, Pa. [u.a.]
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Please use a persistent id in citations: doi:10.1158/1078-0432.CCR-21-2057
Abstract: International consensus and the 2021 WHO classification recognize eight molecular subgroups among non-WNT/non-SHH (Group 3/4) medulloblastoma, representing ~60% of tumors. However, very few clinical centers worldwide possess the technical capabilities to determine DNA-methylation profiles or other molecular parameters of high-risk for Group 3/4 tumors. As a result, biomarker-driven risk stratification and therapy assignment constitutes a major challenge in medulloblastoma research. Here, we identify an immunohistochemistry (IHC) marker as a clinically tractable method for improved medulloblastoma risk stratification.We bioinformatically analyzed published medulloblastoma transcriptomes and proteomes identifying as a potential biomarker TPD52, whose IHC prognostic value was validated across three Group 3/4 medulloblastoma clinical cohorts (n = 387) treated with conventional therapies.TPD52 IHC positivity represented a significant independent predictor of early relapse and death for Group 3/4 medulloblastoma (HRs between 3.67-26.7 [95% CIs between 1.00-706.23], p = 0.05, 0.017 and 0.0058). Cross-validated survival models incorporating TPD52 IHC with clinical features outperformed existing state-of-the-art risk stratification schemes, and reclassified ~50% of patients into more appropriate risk categories. Finally, TPD52 immunopositivity was a predictive indicator of poor response to chemotherapy (HR 12.66 [95% CI 3.53-45.40], p < 0.0001), suggesting important implication for therapeutic choices.The current study redefines the approach to risk stratification in Group 3/4 medulloblastoma in global practice. Since integration of TPD52 IHC in classification algorithms significantly improved outcome prediction, this test could be rapidly adopted for risk stratification on a global scale, independently of advanced but technically challenging molecular profiling techniques.
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