Microarray-based determination of estrogen receptor, progesterone receptor, and HER2 receptor status in breast cancer.

Author(s): Roepman P, Horlings HM, Krijgsman O, Kok M, Bueno-de-Mesquita JM, Bender R, Linn SC, Glas AM, van de Vijver MJ

Publication: Clin Cancer Res, 2009, Vol. 15, Page 7003-11

PubMed ID: 19887485 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 IHC scoring method, analysis of whole sections rather than TMAs, and evaluation by IHC versus chromogenic in situ hybridization (CISH) on the concordance of ER, PR and HER2 status of breast tumors. Results were compared with those obtained by DNA microarray. For the tissue microarrays, 3 cores were examined per case, and ER and PR IHC positivity was defined as more than 10% of tumor cells staining (central scoring). HER2 IHC was scored on a 4 point scale with positivity defined as complete membrane staining in more than 10% of cells. HER2 CISH was used to determine HER2 status of borderline cases with positivity defined as at least 6 CISH spots.

   Summary of Findings:

   IHC results using central scoring and DNA microarray results were strongly correlated (r=0.77, 0.61, and 0.76 for ER, PR and HER2, respectively) with agreement of results in 93, 83 and 96% of cases for ER, PR and HER2 respectively. Non-concordant results for ER and PR generally arose from positive microarray results and negative immunohistochemical scoring, while the reverse was true for HER2 status. In cases that were preselected based on high concordance of IHC results between local and central scoring methods, concordance rates between DNA microarray results and IHC results in whole sections using local, central and ASCO/CAP scores were 92, 93 and 92%, respectively for ER, 84, 81, and 86%, respectively for PR, and 93, 95 and 94%, respectively for HER2. Concordance rates were similarly high between DNA microarrays and IHC staining of TMAs or whole sections. Of 11 cases with discordant IHC results between central and ASCO/CAP scoring, 5 were able to be classified after DNA microarray analysis.

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Tissue microarray
   Protein	Immunohistochemistry
   DNA	In situ hybridization
   RNA	DNA microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Aliquots and Components	Type of slide	Tissue microarray Whole tissue section
   Immunohistochemistry Specific	Data handling	Local scoring Central scoring ASCO/CAP scoring
   Immunohistochemistry Specific	Targeted peptide/protein	ER PR HER2
   DNA microarray Specific	Targeted nucleic acid	ER PR HER2
   DNA microarray Specific	Technology platform	IHC

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