title: External Quality Assessment (EQA) program for the preanalytical and analytical immunohistochemical determination of HER2 in breast cancer: an experience on a regional scale.
abstract: BACKGROUND
  An External Quality Assessment (EQA) program was developed to investigate the state of the art of HER2 immunohistochemical determination in breast cancer (BC) in 16 Pathology Departments in the Lazio Region (Italy). This program was implemented through two specific steps to evaluate HER2 staining (step 1) and interpretation (step 2) reproducibility among participants.
  
  
  METHODS
  The management activities of this EQA program were assigned to the Coordinating Center (CC), the Revising Centers (RCs) and the Participating Centers (PCs). In step 1, 4 BC sections, selected by RCs, were stained by each PC using their own procedures. In step 2, each PC interpreted HER2 score in 10 BC sections stained by the CC. The concordance pattern was evaluated by using the kappa category-specific statistic and/or the weighted kappa statistic with the corresponding 95% Jackknife confidence interval.
  
  
  RESULTS
  In step 1, a substantial/almost perfect agreement was reached between the PCs for scores 0 and 3+ whereas a moderate and fair agreement was observed for scores 1+ and 2+, respectively.In step 2, a fully satisfactory agreement was observed for 6 out of the 16 PCs and a quite satisfactory agreement was obtained for the remaining 10 PCs.
  
  
  CONCLUSIONS
  Our findings highlight that in the whole HER2 evaluation process the two intermediate categories, scores 1+ and 2+, are less reproducible than scores 0 and 3+. These findings are relevant in clinical practice where the choice of treatment is based on HER2 positivity, suggesting the need to share evaluation procedures within laboratories and implement educational programs.
authors: Pathology Department, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy. mottolese@ifo.it.
authors: Irene
authors: I
authors: Terrenato
authors: Vincenzo
authors: V
authors: Arena
authors: Sara
authors: S
authors: Pizzamiglio
authors: Ilaria
authors: I
authors: Pennacchia
authors: Letizia
authors: L
authors: Perracchio
authors: Simonetta
authors: S
authors: Buglioni
authors: Cristiana
authors: C
authors: Ercolani
authors: Francesca
authors: F
authors: Sperati
authors: Leopoldo
authors: L
authors: Costarelli
authors: Elena
authors: E
authors: Bonanno
authors: Daniela
authors: D
authors: Baldini
authors: Silvia
authors: S
authors: Candia
authors: Anna
authors: A
authors: Crescenzi
authors: Antonella
authors: A
authors: Dal Mas
authors: Claudio
authors: C
authors: Di Cristofano
authors: Vito
authors: V
authors: Gomes
authors: Lucia Rosalba
authors: LR
authors: Grillo
authors: Paola
authors: P
authors: Pasquini
authors: Maria Nicoletta
authors: MN
authors: Pericoli
authors: Maria Teresa
authors: MT
authors: Ramieri
authors: Domenica
authors: D
authors: Di Stefano
authors: Luigi
authors: L
authors: Ruco
authors: Stefania
authors: S
authors: Scarpino
authors: Domenico
authors: D
authors: Vitolo
authors: Giulia
authors: G
authors: d'Amati
authors: Angelo
authors: A
authors: Paradiso
authors: Paolo
authors: P
authors: Verderio
authors: Marcella
authors: M
authors: Mottolese
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011786:Quality Control; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
references: J Exp Clin Cancer Res. 2010 Mar 10;29:23
references: 20214830
references: J Clin Pathol. 2004 Mar;57(3):241-2
references: 14990591
references: Eur J Cancer. 2001 Jan;37 Suppl 1:25-29
references: 11342197
references: J Clin Pathol. 2008 Jun;61(6):757-60
references: 18326010
references: J Clin Oncol. 2007 Aug 1;25(22):e27-8
references: 17664462
references: Clin Cancer Res. 2011 Apr 1;17(7):2055-64
references: 21307144
references: J Clin Oncol. 2007 Jan 1;25(1):118-45
references: 17159189
references: N Engl J Med. 2001 Mar 15;344(11):783-92
references: 11248153
references: Int J Biol Markers. 2005 Jul - Sep;20(3):189-194
references: 28207128
references: Histopathology. 2010 May;56(6):720-6
references: 20546337
references: Arch Pathol Lab Med. 2003 May;127(5):549-53
references: 12708896
references: Am J Epidemiol. 1982 Jun;115(6):841-5
references: 7091143
references: Anal Cell Pathol. 1998;16(2):83-93
references: 9692682
references: Am J Clin Pathol. 2009 Jan;131(1):106-11
references: 19095573
references: Cancer Treat Rev. 2008 Oct;34(6):539-57
references: 18502589
references: N Engl J Med. 2012 Jan 12;366(2):109-19
references: 22149875
references: J Clin Pathol. 2004 Mar;57(3):233-7
references: 14990588
references: Int J Biol Markers. 2004 Apr-Jun;19(2):147-54
references: 15255548
references: Mol Diagn Ther. 2013 Apr;17(2):85-99
references: 23529353
references: N Engl J Med. 2006 Dec 28;355(26):2733-43
references: 17192538
references: N Engl J Med. 2012 Nov 8;367(19):1783-91
references: 23020162
references: Nat Rev Clin Oncol. 2011 Nov 29;9(1):16-32
references: 22124364
references: Mod Pathol. 2007 May;20(5):584-91
references: 17396141
references: Biometrics. 1977 Mar;33(1):159-74
references: 843571