title: Diagnostic value of automated Her2 evaluation in breast cancer: a study on 272 equivocal (score 2+) Her2 immunoreactive cases using an FDA approved system.
abstract: Goal of this study was to asses the performance of Aperio computer-assisted analysis for HER2 immunohistochemical measurement in 292 equivocally (score2+) HercepTest immunoreactive breast cancer cases, evaluated by an experienced pathologist and analyzed with fluorescent in situ hybridization (FISH). The automatic Aperio categorization and the percentage of immunoreactive cells as evaluated by the computer and by the pathologist were recorded. Computer-assisted analysis classified 7 (2.4%) cases as negative (0), 136 (46.6%) as faintly positive (1+), 134 (40.5%) as moderately positive (2+), and 15 (5.1%) as strongly positive (3+). Correlative component analysis (CCA) classification is associated with Her2 amplification (P<0.0001). Compared with the human evaluation, automated CCA classification would save 157 (58%) FISH analyses, while not identifying 15 amplified cases (6% false-negative rate). The mean computer percentage value (CPV) is 18.44% standard deviation ±19.00 (range, 0.01 to 76.10). CPV and the pathologist percentage value are significantly associated and correlated (P<0.001) and have similar sensitivity and specificity in identifying Her2 FISH-amplified cases. CPV has a very low interobserver variation. The difference in CPV in amplified and nonamplified subgroups is statistically significant (P<0.001). Receiver operating characteristic analysis indicates that CPV is good at separating FISH nonamplified from amplified cases (P<0.001). The optimal cut-off value maximizing both sensitivity and specificity is 17.6% (sensitivity=73.3%, specificity=71.6%). Using a different cut-off value (2% of positive cells) we would have missed only 3 amplified cases (1% false-negative rate) while not submitting to FISH 52 cases (18% of the whole series). This false-negative rate is well below the expected false-negative rate usually observed in score 1 cases, supporting the use of CCA with a modified cut-off value in routine diagnostics for equivocally stained HER2 cases.
authors.affiliation: Unit of Surgical Pathology, S. Chiara Hospital, Trento, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cantaloni
authors.forename: Eugenia
authors.initials: E
authors.lastname: Tonini R
authors.forename: Claudio
authors.initials: C
authors.lastname: Eccher
authors.forename: Luca
authors.initials: L
authors.lastname: Morelli
authors.forename: Elena
authors.initials: E
authors.lastname: Leonardi
authors.forename: Emma
authors.initials: E
authors.lastname: Bragantini
authors.forename: Daniela
authors.initials: D
authors.lastname: Aldovini
authors.forename: Silvia
authors.initials: S
authors.lastname: Fasanella
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferro
authors.forename: Daniela
authors.initials: D
authors.lastname: Cazzolli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Berlanda
authors.forename: Paolo
authors.initials: P
authors.lastname: Dalla Palma
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbareschi
mesh_terms: D057205:Automation, Laboratory / Q000295:instrumentation / Q000379:methods; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D018795:Device Approval; D003936:Diagnosis, Computer-Assisted; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014481:United States
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human