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.
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 cancerpatients. 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 cancerpatients 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.
Authors: Kirsten Vang Nielsen; Sven Müller; Susanne Møller; Andreas Schønau; Eva Balslev; Ann S Knoop; Bent Ejlertsen Journal: Mol Oncol Date: 2009-11-18 Impact factor: 6.603
Authors: Gang Ren; Xunzhen Zheng; Matthew Bommarito; Samantha Metzger; Yashna Walia; Joshua Letson; Allen Schroering; Andrea Kalinoski; David Weaver; Christopher Figy; Kam Yeung; Saori Furuta Journal: Sci Rep Date: 2019-04-30 Impact factor: 4.379