J Breast Cancer.  2012 Dec;15(4):381-387. 10.4048/jbc.2012.15.4.381.

HER2 Status by Standardized Immunohistochemistry and Silver-Enhanced In Situ Hybridization in Korean Breast Cancer

• Bae YK
• Gong G
• Kang J
• Lee A
• Cho EY
• Lee JS
• Suh KS
• Lee DW
• Jung WH
• The Breast Pathology Study Group of Korean Society of Pathologists

• KMID: 2286433
• DOI: http://doi.org/10.4048/jbc.2012.15.4.381

Abstract

PURPOSE
Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18% to 20% of breast cancers, and it is recognized as a prognostic and predictive marker. We investigated the HER2 status in Korean breast cancer by immunohistochemistry (IHC) and silver-enhanced in situ hybridization (SISH), as the first step toward building a nationwide quality assurance program for HER2 testing.
METHODS
A total of 1,198 breast carcinoma samples were collected from six institutions and IHC and SISH were performed using tissue microarrays in central laboratories. The results were compared to those of local laboratories.
RESULTS
Available data were obtained from 959 samples. Central IHC results were negative, equivocal, and positive for 756 (78.8%; range among institutions, 76.8-81.8%), 37 (3.9%; 1.9-6.2%), and 166 (17.3%; 13.6-20%), respectively. SISH results were negative, equivocal, and positive for 756 (78.8%; 77.4-79.9%), 2 (0.2%; 0-0.7%), and 201 (21%; 20.1-22.2%), respectively. HER2 gene amplification was observed in 4.4%, 19%, and 73.9% of the negative, equivocal and positive groups stratified by local IHC results, respectively. When central SISH was considered to be the gold standard method for measuring HER2 status, the false-negative and false-positive rates of local IHC were 14.4% (29/201) and 7.1% (54/756). The concordance rate between central IHC and SISH was 98.4%.
CONCLUSION
Central IHC and SISH markedly decreased the interlaboratory variability of HER2 status and the results of the two were highly concordant. The quality control program for HER2 testing must be focused on decreasing both the false negativity and positivity of IHC in local laboratories.

Keyword

Breast neoplasms; HER2 gene; Immunohistochemistry; Silver-enhanced in situ hybridization

MeSH Terms

Breast
Breast Neoplasms
Genes, erbB-2
Humans
Immunohistochemistry
In Situ Hybridization
Quality Control
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Resin Cements
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Resin Cements

Figure

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  Figure 1 Local immunohistochemistry (IHC) (A), central IHC (B), and silver-enhanced in situ hybridization (C) results by institution.

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  Figure 2 Representative examples of discordant results between immunohistochemistry and silver-enhanced in situ hybridization (SISH). One case exhibited (A) negative (0) HER2 immunohistochemistry, but HER2 gene amplification (B) was observed when compared with the chromosome 17 (Chr17) signals (C) in SISH analysis. Another case exhibited (D) positive (3+) HER2 immunohistochemistry, but SISH data were negative for HER2 amplification (E, F). The HER2/Chr17 ratio was 1 (×400).

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