title: A multicentre validation of Metasin: a molecular assay for the intraoperative assessment of sentinel lymph nodes from breast cancer patients.
abstract: OBJECTIVE
  Treatment strategies for breast cancer continue to evolve. No uniformity exists in the UK for the management of node-positive breast cancer patients. Most centres continue to use conventional histopathology of sampled sentinel lymph nodes (SLNs), which requires delayed axillary clearance in up to 25% of patients. Some use touch imprint cytology or frozen section for intraoperative testing, although both have inherent sensitivity issues. An intraoperative molecular diagnostic approach helps to overcome some of these limitations. The aim of this study was to assess the clinical effectiveness of Metasin, a molecular method for the intraoperative evaluation of SLNs.
  
  
  RESULTS
  RNA from 3296 lymph nodes from 1836 patients undergoing SLN assessment was analysed with Metasin. Alternate slices of tissue were examined in parallel by histology. Cases deemed to be discordant were analysed by protein gel electrophoresis. There was concordance between Metasin and histology in 94.1% of cases, with a sensitivity of 92% [95% confidence interval (CI) 88-94%] and a specificity of 97% (95% CI 95-97%). Positive and negative predictive values were 88% and 98%, respectively. Over half of the discordant cases (4.4%) were ascribed to tissue allocation bias (TAB).
  
  
  CONCLUSIONS
  Clinical validation of the Metasin assay suggests that it is sufficiently sensitive and specific to make it fit for purpose in the intraoperative setting.
authors.affiliation: Breast Care Unit, Prince Philip Hospital, Llanelli, UK.
authors.forename: Priya
authors.initials: P
authors.lastname: Sai-Giridhar
authors.affiliation: Barts and the Royal London Hospital, London, UK.
authors.forename: Salma
authors.initials: S
authors.lastname: Al-Ramadhani
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Dilushana
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authors.lastname: George
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Preethi
authors.initials: P
authors.lastname: Gopinath
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK.
authors.forename: William
authors.initials: W
authors.lastname: Andrews
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Samar
authors.initials: S
authors.lastname: Jader
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Shelley
authors.initials: S
authors.lastname: Brown
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Findlay
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Evdokia
authors.initials: E
authors.lastname: Arkoumani
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Salam
authors.initials: S
authors.lastname: Al-Sam
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Jolanta G
authors.initials: JG
authors.lastname: McKenzie
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Howard
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authors.lastname: Bradpiece
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jenkins
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Aylwin
authors.affiliation: Breast Care Unit, Prince Philip Hospital, Llanelli, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Holt
authors.affiliation: Breast Care Unit, Prince Philip Hospital, Llanelli, UK.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Sharaiha
authors.affiliation: Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Yiangou
authors.affiliation: Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: Avi
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authors.lastname: Agrawal
authors.affiliation: Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: McDowell
authors.affiliation: Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: Francis G
authors.initials: FG
authors.lastname: Gabriel
authors.affiliation: Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: Margaret
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authors.lastname: Jeffrey
authors.affiliation: Queen Alexandra Hospital, Portsmouth, UK.
authors.forename: Neerja
authors.initials: N
authors.lastname: Agrawal
authors.affiliation: Department of Pathology, Warwick Medical School, University Hospitals Coventry and Warwickshire, Warwick, UK.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cree
authors.affiliation: Cardiff University, Cardiff, UK.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Mansel
authors.affiliation: Royal Free Hospital, London, UK.
authors.forename: Mo
authors.initials: M
authors.lastname: Keshtgar
authors.affiliation: Royal Free Hospital, London, UK.
authors.forename: Nuala
authors.initials: N
authors.lastname: McDermott
authors.affiliation: Royal Free Hospital, London, UK.
authors.forename: Soha
authors.initials: S
authors.lastname: El Sheikh
authors.affiliation: University of Hertfordshire, Hatfield, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wellsted
authors.affiliation: University of Hertfordshire, Hatfield, UK.
authors.forename: Jade
authors.initials: J
authors.lastname: Collard
authors.affiliation: University of Hertfordshire, Hatfield, UK.
authors.forename: Hema
authors.initials: H
authors.lastname: Chaplin
authors.affiliation: TIB MOLBIOL Syntheselabor, Berlin, Germany.
authors.forename: Olfert
authors.initials: O
authors.lastname: Landt
authors.affiliation: Postgraduate Medical Institute, Faculty of Medical Science, Anglia Ruskin University, Chelmsford, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bustin
authors.affiliation: Department of Pathology, Southend University Hospital NHS Trust, Southend, UK.
authors.forename: Maryse
authors.initials: M
authors.lastname: Sundaresan
authors.affiliation: Princess Alexandra Hospital NHS Trust, Harlow, UK.
authors.forename: Vasi
authors.initials: V
authors.lastname: Sundaresan
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D000071036:Sentinel Lymph Node / Q000473:pathology*; D021701:Sentinel Lymph Node Biopsy / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor
keywords: CK19; Metasin; PCR; axillary clearance; breast cancer; intraoperative; mammaglobin; molecular; sensitivity; sentinel lymph node; specificity