Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab

• Published in: Breast cancer research and treatment Vol. 93; no. 1; pp. 3 - 11
• Main Authors: DYBDAL, Noël, LEIBERMAN, Grazyna, ANDERSON, Steven, MCCUNE, Bryan, BAJAMONDE, Alex, COHEN, Robert L, MASS, Robert D, SANDERS, Corsee, PRESS, Michael F
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.09.2005; Springer Nature B.V
• Subjects: Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Chemotherapy; Clinical trials; Clinical Trials as Topic; Female; Fluorescence in situ hybridization; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes; Genes, erbB-2 - genetics; Gynecology. Andrology. Obstetrics; Humans; Immunoassay; Immunohistochemistry; In Situ Hybridization, Fluorescence; Mammary gland diseases; Medical sciences; Neoplasm Metastasis; Paraffin Embedding; Pharmacology. Drug treatments; Predictive Value of Tests; Trastuzumab; Tumors; Women; Antineoplastic agent; Immunohistochemistry; fluorescence in situ hybridization (FISH); erbB2 Gene; Monoclonal antibody; Metastasis; metastatic breast cancer (MBC); Anticytokine; Fluorescence in situ hybridization; Adult; Clinical trial; Female; Advanced stage; Protooncogene; Quantitative analysis; Human; immunohistochemistry (IHC); Breast cancer; Malignant tumor; Human Epidermal growth factor Receptor 2; Mammary gland diseases; Gene amplification; Treatment; Concordance; C-Onc gene; HER2; Trastuzumab
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-004-6275-8

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. 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. 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. 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.