ArticleVirchows Archiv : an international journal of pathology2015
Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors.
Article in Virchows Archiv : an international journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Revisiting Ki-67 Assessment in Canine Mast Cell Tumours: From Manual Hotspot to Automated Global Analysis.Veterinary sciences · 2026Article
- Comparison of Mitotic Count and Ki-67 Index in Grading Gastroenteropancreatic Neuroendocrine Tumors and Their Association with Metastases.Biomedicines · 2025Article
- Potential of Proliferative Markers in Pancreatic Cancer Management: A Systematic Review.Health science reports · 2025Review
- Molecular characteristics of early-onset pancreatic ductal adenocarcinoma.Molecular oncology · 2024Article
- Exploration of Digital Image Analysis for Ki67 Quantification in the Grading of Medullary Thyroid Carcinoma: A Pilot Study with 85 Cases.Head and neck pathology · 2023Article
- Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future.Endocrine pathology · 2023Review
- Unsuccessful external validation of the MAC-score for predicting increased MIB-1 index in patients with spinal meningiomas.Frontiers in oncology · 2022Article
- Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms.Cancers · 2021Article
- Ki67 Quantitative Interpretation: Insights using Image Analysis.Journal of pathology informatics · 2019Article
- Fit-for-Purpose Immunohistochemical Biomarkers.Endocrine pathology · 2018Review
- Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms.Virchows Archiv : an international journal of pathology · 2018Review
- Synaptophysin-Ki67 double stain: a novel technique that improves interobserver agreement in the grading of well-differentiated gastrointestinal neuroendocrine tumors.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
- Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index.Endocrine pathology · 2016Article
- The ENETS/WHO grading system for neuroendocrine neoplasms of the gastroenteropancreatic system: a review of the current state, limitations and proposals for modifications.International journal of endocrine oncology · 2016Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability. However, no data exist regarding interlaboratory reproducibility for low proliferation indices which are of importance to discriminate between G1 and G2 NET. We performed MIB1 staining in three different university hospital-based pathology laboratories on a tissue micro array (TMA) of a well-characterized patient cohort, containing pancreatic NET of 61 patients. To calculate the proliferation index, number of positive tumor nuclei was divided by the total number of tumor nuclei. Labeling index was compared to mitotic counts in whole tissue sections and to clinical outcome. Linear regression analysis, intraclass comparison, and log-rank analysis were performed. Intraclass correlation showed moderate-to-fair agreement. Especially low proliferating tumors were affected by interlaboratory differences. Log-rank analysis was performed for each lab and resulted in three different cutoffs (5.0, 3.0, and 0.5 %). Every calculated cutoff stratified the patient cohort to a significant extent for the underlying stain (p < 0.001, <0.001, and <0.001) but showed no or lesser significance when applied to the other stains. Significant and relevant interlab differences for MIB1 exist. Since the MIB1 proliferation index influences grading, local cutoffs or external standardization should urgently be introduced to achieve reliability and reproducibility.
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