Poor Concordance among Nine Immunohistochemistry Classifiers of Cell-of-Origin for Diffuse Large B-Cell Lymphoma: Implications for Therapeutic Strategies
| Autor: | Andrew Wilson, José Cabeçadas, Andrew Owen, Abigail M. Lee, John G. Gribben, Maria Gomes da Silva, Andrew Clear, Janet Matthews, Maria Calaminici, Rute Alvarez, Rita Coutinho |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Pathology Biopsy Concordance Kaplan-Meier Estimate Article Bortezomib hemic and lymphatic diseases Internal medicine Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor medicine Humans Pathology Molecular business.industry Cancer Gold standard (test) Prognosis medicine.disease BCL6 Boronic Acids Immunohistochemistry Lymphoma Gene Expression Regulation Neoplastic Pyrazines Rituximab Lymphoma Large B-Cell Diffuse business Diffuse large B-cell lymphoma medicine.drug |
| Zdroj: | Clinical Cancer Research. 19:6686-6695 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-13-1482 |
| Popis: | Purpose: The opportunity to improve therapeutic choices on the basis of molecular features of the tumor cells is on the horizon in diffuse large B-cell lymphoma (DLBCL). Agents such as bortezomib exhibit selective activity against the poor outcome activated B-cell type (ABC) DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. Although molecular studies are considered gold standard, several immunohistochemistry (IHC) algorithms have been published that claim to be able to stratify patients according to their cell-of-origin and to be relevant for patient outcome. However, results are poorly reproducible by independent groups. Experimental Design: We investigated nine IHC algorithms for molecular classification in a dataset of DLBCL diagnostic biopsies, incorporating immunostaining for CD10, BCL6, BCL2, MUM1, FOXP1, GCET1, and LMO2. IHC profiles were assessed and agreed among three expert observers. A consensus matrix based on all scoring combinations and the number of subjects for each combination allowed us to assess reliability. The survival impact of individual markers and classifiers was evaluated using Kaplan–Meier curves and the log-rank test. Results: The concordance in patient's classification across the different algorithms was low. Only 4% of the tumors have been classified as germinal center B-cell type (GCB) and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP (rituximab plus cyclophosphamide–adriamycin–vincristine–prednisone)–treated cohort. Conclusion: Further work is required to standardize IHC algorithms for DLBCL cell-of-origin classification for these to be considered reliable alternatives to molecular-based methods to be used for clinical decisions. Clin Cancer Res; 19(24); 6686–95. ©2013 AACR. |
| Databáze: | OpenAIRE |
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