title: Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study.
abstract: BACKGROUND
  In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate.
  
  
  METHODS
  544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology.
  
  
  RESULTS
  31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method.
  
  
  CONCLUSIONS
  Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate.
authors.affiliation: Department of Pathology, St Andrea University Hospital, Rome, Italy. Armando.Bartolazzi@ki.se
authors.forename: Armando
authors.initials: A
authors.lastname: Bartolazzi
authors.forename: Fabio
authors.initials: F
authors.lastname: Orlandi
authors.forename: Enrico
authors.initials: E
authors.lastname: Saggiorato
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Federico
authors.initials: F
authors.lastname: Arecco
authors.forename: Ruth
authors.initials: R
authors.lastname: Rossetto
authors.forename: Nicola
authors.initials: N
authors.lastname: Palestini
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Gianni
authors.initials: G
authors.lastname: Bussolati
authors.forename: Marco Paolo
authors.initials: MP
authors.lastname: Martegani
authors.forename: Federico
authors.initials: F
authors.lastname: Pantellini
authors.forename: Angelo
authors.initials: A
authors.lastname: Carpi
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Giovagnoli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Monti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Toscano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sciacchitano
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Pennelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Mian
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Pelizzo
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
authors.forename: Lucio
authors.initials: L
authors.lastname: Palombini
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Aldo
authors.initials: A
authors.lastname: Vecchione
authors.forename: Rino
authors.initials: R
authors.lastname: Bellocco
mesh_terms: D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D005260:Female; D037502:Galectin 3 / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D016606:Thyroid Nodule / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy; D019564:Unnecessary Procedures
chemical_list: D037502:Galectin 3