title: Evaluation of the Metasin assay for intraoperative assessment of sentinel lymph node metastases in breast cancer.
abstract: OBJECTIVE
  Sentinel lymph node (SLN) biopsy is the preferred surgical technique for staging the axilla in clinically node-negative breast cancer. Accurate intraoperative staging allows for the immediate performance of an axillary clearance in node-positive patients. We assessed the Metasin assay for the intraoperative analysis of SLNs in a prospective evaluation of 250 consecutive patients undergoing intraoperative SLN analysis at the Breast Unit, University Hospital, Southampton, UK.
  
  
  METHODS
  Metasin uses a quantitative reverse transcription PCR to detect two markers of metastasis: cytokeratin 19 (CK19) an epithelial marker and mammaglobin (MGB) a breast specific marker. Metasin results were compared with the results from routine paraffin block histopathology.
  
  
  RESULTS
  Metasin was robust, with a failure rate of <1%, and demonstrated excellent accuracy and reproducibility. The average turnaround time for the Metasin assay was 42 min, the largest variable being the number of nodes assayed. A total of 533 SLNs were evaluated with 75 patients testing positive for MGB and/or CK19. Based on the analysis of individual SLNs, the overall concordance between Metasin and histology was 92.3% (sensitivity 88.7%, specificity 92.9%). When adjusted for tissue allocation bias, the concordance was 93.8% (sensitivity 89.8%, specificity 94.6%). In this evaluation, 57/250 patients (23%) proceeded to axillary clearance based on Metasin results and were considered spared a second operative procedure.
  
  
  CONCLUSIONS
  Metasin has proven to be an accurate, reproducible and reliable laboratory test. The analysis time is acceptable for intraoperative use, and in comparison to routine histology demonstrates acceptable concordance, sensitivity and specificity.
authors.affiliation: Department of Molecular Pathology, University Hospital Southampton, Southampton, UK.
authors.forename: G J
authors.identifier: http://orcid.org/0000-0003-1187-4849
authors.initials: GJ
authors.lastname: Smith
authors.affiliation: Department of Immunology & Molecular Pathology, University Hospital Southampton, Southampton, UK.
authors.forename: E
authors.initials: E
authors.lastname: Hodges
authors.affiliation: University Hospital Southampton, Cellular Pathology, Southampton, UK.
authors.forename: H
authors.initials: H
authors.lastname: Markham
authors.affiliation: Department of Molecular Pathology, University Hospital Southampton, Southampton, UK.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: University of Southampton, Cancer Sciences, Faculty of Medicine and University Hospital Southampton, Southampton Breast Unit, Southampton, UK.
authors.forename: R I
authors.initials: RI
authors.lastname: Cutress
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology*; D060785:Mammaglobin A / Q000235:genetics / Q000378:metabolism; D016343:Monitoring, Intraoperative; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000071036:Sentinel Lymph Node / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D060785:Mammaglobin A
keywords: BREAST CANCER; MOLECULAR PATHOLOGY; SENTINEL NODE