Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors

Blank, Annika; Wehweck, Laura; Marinoni, Ilaria; Boos, Laura Amanda Meret Sophie; Bergmann, Frank; Schmitt Kurrer, Anja; Perren, Aurel (2015). Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors. Virchows Archiv, 467(5), pp. 543-550. Springer 10.1007/s00428-015-1843-3

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Cytopathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Autopsy

UniBE Contributor:

Blank, Annika; Wehweck, Laura; Marinoni, Ilaria; Boos, Laura Amanda Meret Sophie; Schmitt Kurrer, Anja and Perren, Aurel

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0945-6317

Publisher:

Springer

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

18 Jan 2016 16:44

Last Modified:

18 Jan 2016 16:44

Publisher DOI:

10.1007/s00428-015-1843-3

PubMed ID:

26384025

Uncontrolled Keywords:

Interlaboratory variability, MIB1, Ki67, Neuroendocrine, Grading

BORIS DOI:

10.7892/boris.74597

URI:

https://boris.unibe.ch/id/eprint/74597

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