title: Predictors of human epidermal growth factor receptor 2 fluorescence in-situ hybridisation amplification in immunohistochemistry score 2+ infiltrating breast cancer: a single institution analysis.
abstract: OBJECTIVE
  Eligibility for anti-human epidermal growth factor receptor 2 (HER2) treatments in breast cancer requires a correct HER2 status assessment. Testing guidelines recommend fluorescence in-situ hybridisation (FISH) for samples scored as 2+ by immunohistochemistry. This study investigates the correlation between pathological features and FISH amplification in HER2 2+ breast cancer cases.
  
  
  METHODS
  480 HER2 2+ breast cancer samples were included. The association between tumour grade, hormone receptor status, proliferation index (Ki67) and FISH amplification, using both US Food and Drug Administration (ratio ≥2) and American Society of Clinical Oncologists/College of American Pathologists cut-offs (ratio >2.2) was evaluated.
  
  
  RESULTS
  90.2% of the samples were hormone receptor positive. The median Ki67 value was 23.5%; 311 (64.8%) samples showed a Ki67 value of 15% or greater. Tumour grade was evaluable in 421 cases (87.7%), 268 (55.8%) being grade 3. FISH amplification rates were 27.5% (ratio ≥2.0) and 20.8% (ratio >2.2). Grade 3 tumours were more frequently amplified than grades 1-2 tumours: 34% versus 18% (ratio ≥2.0, p<0.001) and 27% versus 9% (ratio >2.2, p<0.001). Samples with Ki67 of 15% or greater showed higher amplification rates than low Ki67 samples: 31% versus 21% (ratio ≥2.0, p=0.022) and 25% versus 12% (ratio >2.2, p=0.003). The OR for FISH amplification was significant in the case of grade 3 and high Ki67 with both cut-offs.
  
  
  CONCLUSIONS
  In this study, high tumour grade and high Ki67 significantly predicted FISH amplification in 480 HER2 2+ breast cancer samples.
authors.affiliation: Department of Oncology, Hematology and Respiratory Diseases, University Hospital, Modena, Italy. vitti10@hotmail.com
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Dieci
authors.forename: Elena
authors.initials: E
authors.lastname: Barbieri
authors.forename: Stefania
authors.initials: S
authors.lastname: Bettelli
authors.forename: Federico
authors.initials: F
authors.lastname: Piacentini
authors.forename: Claudia
authors.initials: C
authors.lastname: Omarini
authors.forename: Guido
authors.initials: G
authors.lastname: Ficarra
authors.forename: Sara
authors.initials: S
authors.lastname: Balduzzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Conte
authors.forename: Valentina
authors.initials: V
authors.lastname: Guarneri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human