Proficiency testing of immunohistochemical biomarker assays in breast cancer.

Author(s): von Wasielewski R, Hasselmann S, Rüschoff J, Fisseler-Eckhoff A, Kreipe H

Publication: Virchows Arch, 2008, Vol. 453, Page 537-43

PubMed ID: 18958494 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to determine the effects of biomarker level, observer and testing laboratory on the determination of ER, PR and HER2 in breast tumors using tissue microarrays. Allred scores were determined for ER and PR, and cases were separated into negative, low, medium, or high expression based on the Allred score. HER2 staining was assigned a score of 0-3. Each of 4 TMAs contained 20-24 cases and was evaluated by 142 laboratories. Fixation method was unspecified but assumed to be formalin.

   Summary of Findings:

   A strong agreement was found between pathologists and reviewers with interobserver kappa scores of 0.84, 0.81, and 0.86 for ER, PR and HER2, respectively, for a single section of one TMA. Further, interobserver agreement was not influenced by score. Reproducible detection of high-expressing ER and PR was achieved by 86% of participants, and more than 92% of participants accurately detected HER2 with a score of 3+, but low expressing ER and PR were only correctly assigned by 61 and 75% of laboratories, respectively, and equivocal HER2 was only scored properly in 41% of laboratories. Over the 4 years of the study, accuracy improved for identification of low expressing and equivocal cases but still lagged behind proper identification of high-expressing cases. Repeat participation also increased performance (p<0.001) with 10.8%, 33.1%, and 24.9% improvements in proper assignment of low-expressing or equivocal cases for ER, PR and HER2, respectively.

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Immunohistochemistry
   Protein	Tissue microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Biomarker level	ER negative Low-expressing ER Medium-expressing ER High-expressing ER PR negative Low-expressing PR Medium-expressing PR High-expressing PR HER2 negative HER2 1+ HER2 2+ HER2 3+
   Biospecimen Acquisition	Time of biospecimen collection	2003 2004 2005 2006
   Immunohistochemistry Specific	Targeted peptide/protein	ER PR HER2

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