title: The first Canadian experience with the Afirma® gene expression classifier test.
abstract: BACKGROUND
  Thyroid nodules are common and often benign, although prove to be malignant upon surgical pathology in 5-15% of cases. When assessed with ultrasound-guided fine-needle aspiration (USFNA), 15-30% of the nodules yield an indeterminate result. The Afirma® gene expression classifier (AGEC) was developed to improve management of indeterminate thyroid nodules (ITNs) by classifying them as "benign" or "suspicious." Objectives were (1) to assess the performance of the AGEC in two Canadian academic medical centres (2), to search for inter-institutional variation and (3) to compare AGEC performance in Canadian versus American institutions.
  
  
  METHODS
  We undertook a retrospective cohort study of patients with indeterminate cytopathology (Bethesda Class III or IV) as per USFNA who underwent AGEC testing. We reviewed patient demographics, cytopathological results, AGEC data and, if the patient underwent surgery, results from their final pathology.
  
  
  RESULTS
  In total, we included 172 patients with Bethesda Class III or IV thyroid nodules underwent AGEC testing, 109 in Montreal, Quebec and 63 in St. John's, Newfoundland, in this study. Among the nodules sent for testing, 55% (60/109) in Montreal and 46% (29/63) in St. John's returned as "benign." None of these patients underwent surgery. On the other hand, 45% (49/109) nodules in Montreal and 54% (34/63) in St. John's were found to be "suspicious," for a total of 83 specimens. Seventy seven of these patients underwent surgery. Both in Montreal and St. John's, the final pathology yielded malignant thyroid disease in approximately 50% of the specimens categorized as "suspicious." Since 2013, no patient diagnosed with a benign nodule as per AGEC testing was found to harbor a malignant thyroid nodule on follow-up.
  
  
  CONCLUSIONS
  Molecular analysis is increasingly used in the management of indeterminate thyroid nodules. This study highlights the experience of two Canadian centres with AGEC testing. We found inter-institutional variability in the rate of nodules returning as "benign," however we found similar rates of confirmed malignancy in nodules returning as "suspicious." According the literature, results for AGEC testing in two Canadian institutions align with results reported in American centres.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, McGill University, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montréal, QC, H3T 1E2, Canada.
authors.forename: Emily
authors.identifier: http://orcid.org/0000-0002-4085-4532
authors.initials: E
authors.lastname: Kay-Rivest
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Memorial University, St. Clare's Mercy Hospital, St. John's, NF, Canada.
authors.forename: Jamie
authors.initials: J
authors.lastname: Tibbo
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, McGill University, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montréal, QC, H3T 1E2, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bouhabel
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, McGill University, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Tamilia
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, University of Montreal, Montreal, QC, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Leboeuf
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, McGill University, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montréal, QC, H3T 1E2, Canada.
authors.forename: Veronique-Isabelle
authors.initials: VI
authors.lastname: Forest
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, McGill University, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montréal, QC, H3T 1E2, Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hier
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Memorial University, St. Clare's Mercy Hospital, St. John's, NF, Canada.
authors.forename: Loren
authors.initials: L
authors.lastname: Savoury
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, McGill University, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montréal, QC, H3T 1E2, Canada. rkpayne@sympatico.ca.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Payne
mesh_terms: D044963:Biopsy, Fine-Needle; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000295:instrumentation*; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods*; D008297:Male; D009523:Newfoundland and Labrador; D011237:Predictive Value of Tests; D011792:Quebec; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis / Q000473:pathology*
keywords: Afirma® Gene Expression Classifier; Indeterminate thyroid nodules; Molecular testing; Thyroid cancer; Ultrasound-guided fine-needle aspiration