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Your search keyword '"Molecular risk factors"' showing total 3 results
Start Over Descriptor "Molecular risk factors" Topic biomarkers, tumor
3 results on '"Molecular risk factors"'

1. Validation of a Molecular Risk Score for Prognosis of Patients With Acute Promyelocytic Leukemia Treated With All-trans Retinoic Acid and Chemotherapy-containing Regimens.

Author

Hecht A, Doll S, Altmann H, Nowak D, Lengfelder E, Röllig C, Ehninger G, Spiekermann K, Hiddemann W, Weiß C, Hofmann WK, Nolte F, and Platzbecker U

Subjects
Adult, Aged, Aged, 80 and over, Cohort Studies, Disease-Free Survival, Female, Gene Expression Regulation, Leukemic, Humans, Leukemia, Promyelocytic, Acute diagnosis, Leukemia, Promyelocytic, Acute genetics, Male, Middle Aged, Neoplasm Proteins genetics, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care statistics & numerical data, Prognosis, Proportional Hazards Models, Risk Factors, Transcriptional Regulator ERG genetics, WT1 Proteins genetics, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor genetics, Leukemia, Promyelocytic, Acute drug therapy, Tretinoin therapeutic use
Abstract

Introduction: Although treatment of acute promyelocytic leukemia (APL) has evolved dramatically during the past decades, especially with the introduction of all-trans retinoic acid, risk stratification remains an important issue. To date, relapse risk can be predicted by leukocyte and platelet counts only. In the present report, we present a validation study on 3 candidate genes and a newly developed molecular risk score for APL in 2 independent patient cohorts., Patients and Methods: An integrative risk score combining the expression levels of BAALC, ERG, and WT1 was calculated for 79 de novo APL patients from the original cohort and 76 de novo APL patients from a validation cohort. Gene expression analysis was executed the same for both cohorts, and the results regarding the effect on patient outcomes were compared., Results: The expression levels of BAALC, ERG, and WT1 were similar in both cohorts compared with the healthy controls. The relapse and survival rates were not different between the low- and high-risk patients according to the Sanz score. However, application of the molecular risk score on the validation cohort distinctly discriminated patients according to their risk of relapse and death just as in the original APL cohort, although single gene analyses could not reproduce the negative prognostic impact., Conclusion: The analysis clearly validated the prognostic effect of the integrative risk score on the outcome in APL patients. The value was further empowered because the single gene analyses did not show similar results. Whether the integrative risk score retains its prognostic power in the chemotherapy-free setting should be investigated further., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2017
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2. Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment

Author

Leon-Castillo, A., Horeweg, N., Peters, E.E.M., Rutten, T., Haar, N. ter, Smit, V.T.H.B.M., Kroon, C.D., Boennelycke, M., Hogdall, E., Hogdall, C., Nout, R.R.A., Creutzberg, C.L., Ortoft, G., and Bosse, T.

Subjects
Lymphovascular space invasion, Obstetrics and Gynecology, Lymphadenectomy, Prognosis, Endometrial Neoplasms, Endometrial cancer, Oncology, Mutation, Biomarkers, Tumor, Humans, Lymph Node Excision, Female, Tumor Suppressor Protein p53, Molecular risk factors
Abstract

Introduction: The clinical role of the molecular endometrial cancer (EC) classification has not been fully explored in patients staged with lymphadenectomy or without adjuvant treatment, conditions that could potentially moderate the prognostic value of the classification. We aimed to evaluate the clinical outcome of the molecular subgroups in patients with high-grade EC staged by lymphadenectomy and those without adjuvant treatment.Methods: DNA-sequencing for the detection of pathogenic POLE-exonuclease domain mutations and immunohistochemistry for mismatch repair (MMR) proteins and p53 expression were performed on 412 high-grade EC from the Danish Gynaecological Cancer Database (2005-2012) to classify them as POLE-ultramutated (POLEmut), MMR-deficient (MMRd), p53-mutant (p53abn), or no specific molecular profile (NSMP). Patients with stage IV or residual disease after surgery were excluded. Kaplan-Meier method, log-rank test and Cox proportional hazard models were used for analysis.Results: Molecular analysis was successful in 367 EC; 251 patients had undergone lymphadenectomy. Five-year recurrence rates in this subgroup of patients was 36.7% for women with p53abn EC, 0.0% for POLEmut EC, 13.4% for MMRd EC and 42.9% for NSMP EC (p < 0.001). Similar results were observed among stage IA-IB patients. Among patients without adjuvant treatment (n = 264), none with POLEmut EC (n = 26) had a recurrence.Conclusion: The molecular EC classification has strong prognostic value, independent of clinicopathological factors, also among high-grade EC patients staged by lymphadenectomy and those without adjuvant treatment. The unfavourable prognosis of early-stage p53abn EC is not due to undetected lymph node metastasis, and the indolent behaviour of POLEmut EC is independent of adjuvant treatment.

Published
2022
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3. Selecting Adjuvant Treatment for Endometrial Carcinoma Using Molecular Risk Factors

Author

Carien L. Creutzberg, Bastiaan G Wortman, Tjalling Bosse, and Remi A. Nout

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, law.invention, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Targeted therapies, Randomized controlled trial, Endometrial cancer, law, Risk Factors, Internal medicine, medicine, Carcinoma, Biomarkers, Tumor, Humans, Chemotherapy, Molecular alterations, Gynecologic Cancers (NS Reed, Section Editor), Molecular Targeted Therapy, Molecular risk factors, PARP inhibitors, Selection (genetic algorithm), Radiotherapy, business.industry, Age Factors, Adjuvant treatment, medicine.disease, Prognosis, Endometrial Neoplasms, Radiation therapy, 030104 developmental biology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Mutation, Female, Radiotherapy, Adjuvant, business, Adjuvant, Carcinoma, Endometrioid, Checkpoint inhibitors
Abstract

Purpose of Review To provide an overview of common molecular risk factors in endometrial cancer (EC) with the possibility to improve adjuvant treatment selection. Recent Findings Recent studies have discovered and confirmed four different molecular subclasses in EC, with each having a distinct prognosis; POLE-ultramutated, microsatellite unstable, copy-number low, and copy-number high. Subsequent studies have shown that combining both molecular with clinicopathological risk factors can potentially improve adjuvant treatment selection for women with high-intermediate risk EC. For high risk and advanced stage EC, several molecular alterations are being explored for targeted therapy. Summary Molecular alterations are frequently found in endometrial cancer and have currently not been implemented in the treatment guidelines for EC. Assessment of molecular alterations can distinguish patients that require less or more intensified adjuvant treatment. Trials investigating targeted therapies in EC are ongoing and have shown some promising results, however, more evidence is needed and results of randomized trials have to be awaited.

Published
2019

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