PURPOSE: To evaluate the concordance between HER2 gene amplification, determined by fluorescence in situ hybridization (FISH), and HER2 protein overexpression assessed by an immunohistochemical (IHC) assay. The IHC protocol used was a research assay, known as the Clinical Trial Assay (CTA), developed to select women with metastatic breast cancer (MBC) for three pivotal clinical trials of trastuzumab therapy. METHODS: A direct-labeled, dual-probe FISH assay was used to determine HER2 amplification in 623 fixed breast cancer tissue specimens. These specimens had been stored as paraffin-embedded sections for 25 years. All specimens had been analyzed for HER2 protein expression by the CTA. To assess the reproducibility of FISH results in archived material, we evaluated a separate group of 617 breast cancer tissue specimens at two different laboratories. RESULTS: Informative FISH results were available for 529 (85%) of the 623 specimens. Overall concordance between FISH and IHC results was 82% (95% CI; 7885%). Assay agreement between FISH results and specimens with immunostaining scores of 0, 1+, and 3+ were 97, 93 and 89%, respectively. However, only 24% of specimens with 2+ immunostaining scores had HER2 amplification by FISH; there was assay disagreement in 76% of specimens in this IHC subgroup. Interlaboratory FISH concordance was 92% (95% CI; 8994%), indicating very good assay reproducibility in these archived specimens. CONCLUSION: HER2 status determined by CTA-IHC and FISH are significantly correlated; however, differences between these two assays can a ect patient selection for trastuzumab therapy.
PURPOSE: To evaluate the concordance between HER2 gene amplification, determined by fluorescence in situ hybridization (FISH), and HER2 protein overexpression assessed by an immunohistochemical (IHC) assay. The IHC protocol used was a research assay, known as the Clinical Trial Assay (CTA), developed to select women with metastatic breast cancer (MBC) for three pivotal clinical trials of trastuzumab therapy. METHODS: A direct-labeled, dual-probe FISH assay was used to determine HER2 amplification in 623 fixed breast cancer tissue specimens. These specimens had been stored as paraffin-embedded sections for 25 years. All specimens had been analyzed for HER2 protein expression by the CTA. To assess the reproducibility of FISH results in archived material, we evaluated a separate group of 617 breast cancer tissue specimens at two different laboratories. RESULTS: Informative FISH results were available for 529 (85%) of the 623 specimens. Overall concordance between FISH and IHC results was 82% (95% CI; 7885%). Assay agreement between FISH results and specimens with immunostaining scores of 0, 1+, and 3+ were 97, 93 and 89%, respectively. However, only 24% of specimens with 2+ immunostaining scores had HER2 amplification by FISH; there was assay disagreement in 76% of specimens in this IHC subgroup. Interlaboratory FISH concordance was 92% (95% CI; 8994%), indicating very good assay reproducibility in these archived specimens. CONCLUSION:HER2 status determined by CTA-IHC and FISH are significantly correlated; however, differences between these two assays can a ect patient selection for trastuzumab therapy.
Authors: Rachel Stevens; Imad Almanaseer; Miguel Gonzalez; Derin Caglar; Ryan A Knudson; Rhett P Ketterling; Daniel S Schrock; Thomas A Seemayer; Julia A Bridge Journal: J Mol Diagn Date: 2007-04 Impact factor: 5.568
Authors: Angelo Di Leo; Henry L Gomez; Zeba Aziz; Zanete Zvirbule; Jose Bines; Michael C Arbushites; Stephanie F Guerrera; Maria Koehler; Cristina Oliva; Steven H Stein; Lisa S Williams; Judy Dering; Richard S Finn; Michael F Press Journal: J Clin Oncol Date: 2008-10-27 Impact factor: 44.544
Authors: Elizabeth A Mittendorf; Yun Wu; Maurizio Scaltriti; Funda Meric-Bernstam; Kelly K Hunt; Shaheenah Dawood; Francisco J Esteva; Aman U Buzdar; Huiqin Chen; Sameena Eksambi; Gabriel N Hortobagyi; Jose Baselga; Ana M Gonzalez-Angulo Journal: Clin Cancer Res Date: 2009-11-17 Impact factor: 12.531