Feasibility of using tissue microarrays for the assessment of HER-2 gene amplification by fluorescence in situ hybridization in breast carcinoma Journal Article


Authors: Bhargava, R.; Lal, P.; Chen, B.
Article Title: Feasibility of using tissue microarrays for the assessment of HER-2 gene amplification by fluorescence in situ hybridization in breast carcinoma
Abstract: Tissue microarrays (TMAs) have been commonly used to study protein expression by immunohistochemistry (IHC). However, limited data exist on the validity of using TMAs to study gene amplification. In this study, we evaluated the feasibility of using breast carcinoma TMAs to study HER-2 gene amplification by fluorescence in situ hybridization (FISH). In addition, hormonal receptor status (ER and PR) and HER-2 protein overexpression by IHC were also studied, and results were compared with whole tissue sections. FISH for HER-2 was performed on formalin-fixed paraffin-embedded tissue from 114 invasive breast carcinomas both on whole tissue sections and on TMAs containing the same tumors. The TMA was created using 0.6-mm tissue cores with four sampled cores per tumor from the same tissue block used for whole section FISH. The PathVysion HER-2 probe kit was used for the FISH analysis. A ratio of HER-2:Chromosome 17 ≥2.0 was interpreted as positive for gene amplification. The ER or PR was interpreted as positive when nuclear staining was detected in more than 10% of tumor cells. The HER-2 IHC (HercepTest; DAKO Corp, Carpinteria, CA) results were interpreted as 0, 1+, 2+, and 3+ according to standard criteria. The FISH results in the TMA and whole sections were concordant in 99 out of 101 successfully analyzed cases (99%). The FISH scores were consistent among the two to four cores in the majority of the cases. ER and PR results were concordant between whole sections and TMA cores in 97% (107/110) and 89% (97/109) cases, respectively. The overall concordance for HER-2 status by IHC between whole sections and TMA cores was 86% (94 out of 109 cases). TMAs are a reliable approach to study HER-2 gene amplification in a high throughput manner.
Keywords: immunohistochemistry; controlled study; human tissue; protein expression; validation process; adenocarcinoma; reproducibility of results; in situ hybridization, fluorescence; breast cancer; gene amplification; epidermal growth factor receptor 2; tumor markers, biological; breast neoplasms; fluorescence in situ hybridization; feasibility studies; oligonucleotide array sequence analysis; breast carcinoma; receptor, erbb-2; receptors, estrogen; receptors, progesterone; reliability; cell nucleus; estrogen receptor; progesterone receptor; fish; genes, erbb-2; chromosome 17; formaldehyde; oncogene neu; tissue microarrays; erbb-2; her-2/neu; human; priority journal; article
Journal Title: Diagnostic Molecular Pathology
Volume: 13
Issue: 4
ISSN: 1052-9551
Publisher: Lippincott Williams & Wilkins  
Date Published: 2004-12-01
Start Page: 213
End Page: 216
Language: English
DOI: 10.1097/01.pdm.0000140195.05428.1d
PROVIDER: scopus
PUBMED: 15538111
DOI/URL:
Notes: Diagn. Mol. Pathol. -- Cited By (since 1996):22 -- Export Date: 16 June 2014 -- CODEN: DMPAE -- Source: Scopus
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  1. Beiyun Chen
    49 Chen
  2. Priti Lal
    34 Lal