Tissue microarray technology in the routine assessment of HER-2 status in invasive breast cancer: a prospective study of the use of immunohistochemistry and fluorescence in situ hybridization.

Author(s): Graham AD, Faratian D, Rae F, Thomas JS

Publication: Histopathology, 2008, Vol. 52, Page 847-55

PubMed ID: 18494613 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to compare HER2 IHC staining and FISH between TMAs and whole section slides of breast cancer specimens. Whole section specimens scored as equivocal by IHC (2+), and a subset of those scored as positive (3+) underwent subsequent FISH analysis along with corresponding TMA specimens. 6 cores were included for each of 106 specimens on the TMAs, and scoring was done for specimens with at least 3 assessable cores (103/106). Whole section analysis was repeated for discrepant results between 2 observers until an agreement was reached. The individual core scores were averaged for a TMA specimen score, or HER2 status was determined if at least one core was scored 3+ by IHC staining or had a FISH amplification ratio > 2.0 by both observers.

   Summary of Findings:

   Only 85% and 71% of cases had three assessable TMA cores for IHC and FISH, respectively, when only 3 cores were evaluated, but when 5 cores were evaluated, 3 assessable cores were present for 98% and 95% of specimens, respectively. Complete concordance of HER2 IHC scores for whole sections and TMAs was achieved in 73% of cases when the average of all cores for each case and by each observer was used to determine status. When the highest score was used to determine status, concordance between TMA and whole section HER2 status by IHC was achieved in 78% of cases. Complete concordance in HER2 status by FISH for whole sections and TMAs was achieved in 94.6% of cases when the average of all cores for each case and by each observer was used to determine status. The two discordant cases were HER2+ on the whole section and HER2- on the TMA but were within acknowledged borderline ratios for FISH. When the highest score was used to determine status, concordance between TMA and whole section HER2 status by FISH was achieved in 97% of cases. 96% of specimens that had HER2 scores of 3+ by TMA based IHC staining were also HER2+ by FISH, while 84% of specimens that had HER2 scores of 3+ by whole section IHC staining were HER2+ by FISH.

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Immunohistochemistry
   DNA	FISH
   Protein	Tissue microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Aliquots and Components	Type of slide	Whole section Tissue microarray
   Immunohistochemistry Specific	Targeted peptide/protein	HER2
   FISH Specific	Targeted nucleic acid	HER2 CEN17
   Immunohistochemistry Specific	Technology platform	FISH
   Biospecimen Aliquots and Components	Aliquot size/volume	3 TMA cores evaluated 4 TMA cores evaluated 5 TMA cores evaluated 6 TMA cores evaluated
   Tissue microarray Specific	Data handling	Cores averaged Highest core score

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