title: Does using a higher cutoff for the percentage of positive cells improve the specificity of HER-2 immunohistochemical analysis in breast carcinoma?
abstract: This study was performed to determine whether using a 30% cutoff for the proportion of HER-2+ cells would increase the specificity of HER-2 immunohistochemical analysis. Blinded to the HER-2 amplification status, 3 pathologists retrospectively reviewed HER-2-stained sections of breast carcinoma and considered cases to be positive for protein overexpression (3+) using 3 cutoff levels, 10%, 30%, and 50%, for the proportion of cells with intense uniform staining. Of 98 cases, 27 (28%) were positive by fluorescence in situ hybridization (FISH), and 32 (33%), 28 (29%), and 26 (27%) were considered positive for overexpression using cutoffs of 10%, 30%, and 50%, respectively. The specificity values of HER-2 immunohistochemical analysis were 82%, 86%, and 87% for the different cutoffs, and the concordance rates of 3+ cases with FISH were 59%, 64%, and 65%, for the cutoffs of 10%, 30%, and 50%, respectively. These findings seem to somehow support the recently proposed American Society of Clinical Oncology/College of American Pathologists guideline recommendations for HER-2 testing; nevertheless further studies are suggested.
authors.affiliation: Department of Pathology, University of Alabama School of Medicine, Birmingham 35294-6823, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Hameed
authors.forename: David C
authors.initials: DC
authors.lastname: Chhieng
authors.forename: Amy L
authors.initials: AL
authors.lastname: Adams
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis; D002452:Cell Count; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human