Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study

Armando Bartolazzi, Fabio Orlandi, Enrico Saggiorato, Marco Volante, Federico Arecco, Ruth Rossetto, Nicola Palestini, Ezio Ghigo, Mauro Papotti, Gianni Bussolati, Marco Paolo Martegani, Federico Pantellini, Angelo Carpi, Maria Rosaria Giovagnoli, Salvatore Monti, Vincenzo Toscano, Salvatore Sciacchitano, Gian Maria Pennelli, Caterina Mian, Maria Rosa PelizzoMassimo Rugge, Giancarlo Troncone, Lucio Palombini, Gennaro Chiappetta, Gerardo Botti, Aldo Vecchione, Rino Bellocco

Research output: Contribution to journalArticlepeer-review

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. Findings: 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. Interpretation: 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. Funding: Compagnia di San Paolo, Turin, Italy, and Italian Association for Cancer Research (AIRC), Rome, Italy.

Original languageEnglish
Pages (from-to)543-549
Number of pages7
JournalThe Lancet Oncology
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 2008

ASJC Scopus subject areas

  • Oncology

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