Abstract | OBJECTIVE: Accurate diagnostic assessment of human epidermal growth factor receptor-2 (HER-2) is essential and a prerequisite for appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab ( Herceptin) to the treatment of patients with breast cancer. Immunohistochemistry (IHC) is the most widely applicable diagnostic modality in studying HER-2 status. Fluorescence in situ hybridization (FISH) is also recognized as a modality in cases with an equivocal IHC status (score, 2+). Some authors claimed that FISH alone is sufficient. The aim of this study was to correlate the test results of IHC and FISH for HER-2 gene amplification in breast cancer patients. FISH for topoisomerase IIalpha (TOP2A) was also studied to see if deletion or amplification of TOP2A has any supplementary role to HER-2, FISH and IHC. MATERIALS AND METHODS: Assessment of HER-2 gene amplification and TOP2A gene amplification/deletion was made by FISH analysis using the LSI TOP2A/HER-2/CEP 17 multicolor probe or the LSI HER-2/CEP dual color probe (Vysis, Downers Grove, IL, USA) in formalin-fixed and paraffin-embedded tissue sections of 54 breast cancer patients who were grouped into stages 1+, 2+ or 3+ based on IHC (HercepTest; DakoCytomation, Carpinteria, CA, USA) observations. RESULTS: None of IHC 1+ breast tumors was HER-2 FISH positive, but three of 18 (17%) IHC 3+ tumors were HER-2 FISH negative. Overall, 53% of the IHC 2+ and 83% of the IHC 3+ cases were HER-2 FISH positive. Only one case with IHC 3+ tumor that was HER-2 FISH positive was found to have TOP2A amplification (>2.0) and no IHC 2+ cases were found to have TOP2A amplification. There were no cases with TOP2A deletion (<0.8) in our whole series. There were also no cases of HER-2 FISH negative tumors, but IHC scored as 2+ or 3+ (0 of 10), to be found with TOP2A amplification. The discordance rates by IHC were high (46.7% in IHC 2+, 16.7% in IHC 3+, 30.3% overall in IHC 2+ or 3+). On the contrary, the discordance rates were zero if by FISH. CONCLUSION: The current algorithm to use HER-2 FISH as a supplementary role to IHC HercepTest 2+ may need some modifications according to the local setting. TOP2A FISH adds little value to HER-2 FISH and IHC staining in our study.
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Authors | Shou-Jen Kuo, Boris Bao-Tyan Wang, Cheng-Shyong Chang, Tze-Ho Chen, Kun-Tu Yeh, Dong-Jay Lee, Pao-Lun Yin, Ming Chen |
Journal | Taiwanese journal of obstetrics & gynecology
(Taiwan J Obstet Gynecol)
Vol. 46
Issue 2
Pg. 146-51
(Jun 2007)
ISSN: 1875-6263 [Electronic] China (Republic : 1949- ) |
PMID | 17638622
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antigens, Neoplasm
- DNA-Binding Proteins
- Poly-ADP-Ribose Binding Proteins
- ERBB2 protein, human
- Receptor, ErbB-2
- DNA Topoisomerases, Type II
- TOP2A protein, human
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Topics |
- Antigens, Neoplasm
(genetics, metabolism)
- Breast Neoplasms
(genetics, metabolism, pathology)
- Carcinoma, Ductal, Breast
(genetics, metabolism, pathology)
- Carcinoma, Lobular
(genetics, metabolism, pathology)
- DNA Topoisomerases, Type II
(genetics, metabolism)
- DNA-Binding Proteins
(genetics, metabolism)
- Female
- Gene Amplification
- Gene Deletion
- Gene Expression Regulation, Neoplastic
- Humans
- Immunohistochemistry
- In Situ Hybridization, Fluorescence
- Poly-ADP-Ribose Binding Proteins
- Receptor, ErbB-2
(genetics, metabolism)
- Taiwan
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