AIM: To evaluate the clinical usefulness of three commercially available assays for Her-2/neu oncogene and protein measurements. The Her-2/neu protein is overexpressed, mostly as a result of gene amplification, in 20-30% of human breast cancers, and has been shown to have prognostic and predictive value for treatment with chemotherapy or the new monoclonal antibody, Herceptin. METHODS: An immunohistochemistry (IHC) assay using the Dako polyclonal antibody A0485, which measures the Her-2/neu protein, was compared with two new Food and Drug Administration (FDA) approved fluorescence in situ hybridisation (FISH) assays--INFORM and PathVysion, in a cohort of 52 formalin fixed, paraffin wax embedded breast tissues. These tissues were selected randomly from 84 consecutive infiltrating breast cancer specimens, which were first stratified according to the Her-2/neu protein levels as measured by IHC. RESULTS: The two FISH assays achieved a 98% concordance rate: 14 specimens (27%) showed Her-2/neu gene amplification and 37 specimens (71%) showed no Her-2/neu gene amplification. The PathVysion assay had certain advantages over the INFORM assay. In contrast, the IHC assay detected Her-2/neu overexpression in a high percentage of cases, including 13 high positive specimens (25%) and 13 medium positive specimens (25%). Although 10 of these 13 IHC high positive specimens showed gene amplification by FISH, nine of 13 IHC medium positive specimens showed no gene amplification. Statistical analyses showed that the differences between IHC and FISH assays were primarily in the specimens with medium positive IHC, but negative FISH results. CONCLUSIONS: Because of the increasing importance of the Her-2/neu oncogene and oncoprotein in the clinical management of patients with breast cancer, the accurate and consistent evaluation of Her-2/neu status is crucial. This study suggests that the best approach is to combine both IHC and FISH assays; that is, to use the IHC assay as a triage step, followed by the PathVysion FISH assay to analyse the IHC medium and high positive cases.
AIM: To evaluate the clinical usefulness of three commercially available assays for Her-2/neu oncogene and protein measurements. The Her-2/neu protein is overexpressed, mostly as a result of gene amplification, in 20-30% of humanbreast cancers, and has been shown to have prognostic and predictive value for treatment with chemotherapy or the new monoclonal antibody, Herceptin. METHODS: An immunohistochemistry (IHC) assay using the Dako polyclonal antibody A0485, which measures the Her-2/neu protein, was compared with two new Food and Drug Administration (FDA) approved fluorescence in situ hybridisation (FISH) assays--INFORM and PathVysion, in a cohort of 52 formalin fixed, paraffin wax embedded breast tissues. These tissues were selected randomly from 84 consecutive infiltrating breast cancer specimens, which were first stratified according to the Her-2/neu protein levels as measured by IHC. RESULTS: The two FISH assays achieved a 98% concordance rate: 14 specimens (27%) showed Her-2/neu gene amplification and 37 specimens (71%) showed no Her-2/neu gene amplification. The PathVysion assay had certain advantages over the INFORM assay. In contrast, the IHC assay detected Her-2/neu overexpression in a high percentage of cases, including 13 high positive specimens (25%) and 13 medium positive specimens (25%). Although 10 of these 13 IHC high positive specimens showed gene amplification by FISH, nine of 13 IHC medium positive specimens showed no gene amplification. Statistical analyses showed that the differences between IHC and FISH assays were primarily in the specimens with medium positive IHC, but negative FISH results. CONCLUSIONS: Because of the increasing importance of the Her-2/neu oncogene and oncoprotein in the clinical management of patients with breast cancer, the accurate and consistent evaluation of Her-2/neu status is crucial. This study suggests that the best approach is to combine both IHC and FISH assays; that is, to use the IHC assay as a triage step, followed by the PathVysion FISH assay to analyse the IHC medium and high positive cases.
Authors: D J Slamon; W Godolphin; L A Jones; J A Holt; S G Wong; D E Keith; W J Levin; S G Stuart; J Udove; A Ullrich Journal: Science Date: 1989-05-12 Impact factor: 47.728
Authors: B A Gusterson; R D Gelber; A Goldhirsch; K N Price; J Säve-Söderborgh; R Anbazhagan; J Styles; C M Rudenstam; R Golouh; R Reed Journal: J Clin Oncol Date: 1992-07 Impact factor: 44.544
Authors: P Carter; L Presta; C M Gorman; J B Ridgway; D Henner; W L Wong; A M Rowland; C Kotts; M E Carver; H M Shepard Journal: Proc Natl Acad Sci U S A Date: 1992-05-15 Impact factor: 11.205
Authors: O P Kallioniemi; A Kallioniemi; W Kurisu; A Thor; L C Chen; H S Smith; F M Waldman; D Pinkel; J W Gray Journal: Proc Natl Acad Sci U S A Date: 1992-06-15 Impact factor: 11.205
Authors: S P Naber; Y Tsutsumi; S Yin; S A Zolnay; H Mobtaker; P J Marks; S J McKenzie; R A DeLellis; H J Wolfe Journal: Am J Clin Pathol Date: 1990-08 Impact factor: 2.493
Authors: I O Ellis; J Bartlett; M Dowsett; S Humphreys; B Jasani; K Miller; S E Pinder; A Rhodes; R Walker Journal: J Clin Pathol Date: 2004-03 Impact factor: 3.411
Authors: Azadeh Stark; Celina G Kleer; Iman Martin; Baffour Awuah; Anthony Nsiah-Asare; Valerie Takyi; Maria Braman; Solomon E Quayson; Richard Zarbo; Max Wicha; Lisa Newman Journal: Cancer Date: 2010-11-01 Impact factor: 6.860
Authors: Svetlana Grabauskiene; Edward J Bergeron; Guoan Chen; Andrew C Chang; Jules Lin; Dafydd G Thomas; Thomas J Giordano; David G Beer; Meredith A Morgan; Rishindra M Reddy Journal: Lung Cancer Date: 2013-09-23 Impact factor: 5.705
Authors: Svetlana Grabauskiene; Edward J Bergeron; Guoan Chen; Dafydd G Thomas; Thomas J Giordano; David G Beer; Meredith A Morgan; Rishindra M Reddy Journal: J Surg Res Date: 2013-12-18 Impact factor: 2.192
Authors: I O Ellis; M Dowsett; J Bartlett; R Walker; T Cooke; W Gullick; B Gusterson; E Mallon; P B Lee Journal: J Clin Pathol Date: 2000-12 Impact factor: 3.411