Inter‐ and intra‐observational variability in immunohistochemistry: a multicentre analysis of diffuse large B‐cell lymphoma staining

Lawrie, Charles H.; Ballabio, Erica; Soilleux, Elizabeth; Sington, James; Hatton, Christian S. R.; Dirnhofer, Stephan; Tzankov, Alexandar

doi:10.1111/j.1365-2559.2012.04179.x

Cited by 26 publications

(19 citation statements)

References 21 publications

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“…Although, IHC platform is practical and economical but original publication by Hans et al was short on essential technical details required for reproducibility across institutions, thus impacting global transition into clinical laboratories 29. This may be one of the reasons that initial clinical correlative studies failed to reproduce the survival advantages noted in the original series 30.…”

Section: Discussionmentioning

confidence: 99%

Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

et al. 2017

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AimsThe cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.MethodsDiagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).Results96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).ConclusionsOur report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

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Section: Discussionmentioning

confidence: 99%

Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

et al. 2017

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“…Although many potential reasons for inconsistent results using IHC have been reported (24,37), no definitive procedural consensus is available for implementation in clinical practice. Our study challenges the use of any IHC classifier for subclassification in DLBCL, and it is important to resolve this, as the cell of origin in DLBCL provides not only prognostic information but also offers the window for targeted therapies to improve outcome in this disease.…”

Section: Discussionmentioning

confidence: 99%

Poor Concordance among Nine Immunohistochemistry Classifiers of Cell-of-Origin for Diffuse Large B-Cell Lymphoma: Implications for Therapeutic Strategies

Coutinho

Clear

Owen

et al. 2013

Clinical Cancer Research

107

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Purpose The opportunity to improve therapeutic choices on the basis of molecular features of the tumour 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 DLBCL. In order for targeted therapies to succeed in this disease, robust strategies that segregate patients into molecular groups with high reliability are needed. While 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 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% the tumors have been classified as GCB and 21% as ABC/non-GCB by all methods. None of the algorithms provided prognostic information in the R-CHOP 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.

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“…1 There is an increasing incidence of breast cancer in African countries, including Nigeria; 2 however, the actual burden of the disease is unknown. This is partly because there is no existing national program for early detection and management of the disease.…”

Section: Introductionmentioning

confidence: 99%

Breast Cancer Reporting in Lagos, Nigeria: Implications for Training and Education in Africa

Daramola

Banjo

Bennett

et al. 2016

JGO

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PurposeTo assess the completeness and accuracy of breast cancer pathologic reporting in Nigeria.Materials and MethodsThe histologic parameters provided in breast cancer pathology reports at a large teaching hospital in Nigeria were assessed. The corresponding slides were reviewed after the United Kingdom Royal College of Pathologists guidelines, and results were compared.ResultsOut of 115 breast cancer cases, histologic type of breast carcinoma was concordant with the review type in 53.1% of cases and discordant in 46.9%. Grading was stated in 89.62% of cases, of which 50.5% were correctly graded, 35.8% were under-graded, and 8.5% were over-graded. Poor fixation and omission of the mitotic count were the main reasons for discordant grades. A comment on lymph node status was included in 40% of cases, and lymphovascular invasion was not commented on in 97.4% of cases. Only 26% of the tumors had hormone receptors and/or HER2 tested.ConclusionSome essential histologic parameters were absent from the histologic reports, and where present, a proportion were inaccurate. Attention to specimen fixation and method of grading and familiarity with uncommon breast cancer types are required; all can be facilitated by education and training. The use of a template/proforma is recommended to ensure cancer data set parameters are included in the pathology reports.

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Inter‐ and intra‐observational variability in immunohistochemistry: a multicentre analysis of diffuse large B‐cell lymphoma staining

Abstract: This study suggests that most variability in IHC studies between centres results from inherent limitations of the biomarkers investigated rather than procedural or observational differences.

Cited by 26 publications

References 21 publications

Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

Poor Concordance among Nine Immunohistochemistry Classifiers of Cell-of-Origin for Diffuse Large B-Cell Lymphoma: Implications for Therapeutic Strategies

Breast Cancer Reporting in Lagos, Nigeria: Implications for Training and Education in Africa

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