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Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study - 26/09/12

Doi : 10.1016/S1470-2045(08)70132-3 
Armando Bartolazzi, DrMD a, b, , Fabio Orlandi, MD c, d, Enrico Saggiorato c, d, Marco Volante, MD c, d, Federico Arecco, MD c, d, Ruth Rossetto, MD c, d, Nicola Palestini, MD c, d, Ezio Ghigo, ProfMD c, d, Mauro Papotti, ProfMD c, d, Gianni Bussolati, ProfMD c, d, Marco Paolo Martegani, PhD a, Federico Pantellini, MD e, f, Angelo Carpi, MD e, f, Maria Rosaria Giovagnoli, PhD e, f, Salvatore Monti, MD e, f, Vincenzo Toscano, ProfMD e, f, Salvatore Sciacchitano, MD e, f, Gian Maria Pennelli, MD g, h, Caterina Mian, MD g, h, Maria Rosa Pelizzo, MD g, h, Massimo Rugge, ProfMD g, h, Giancarlo Troncone, MD i, Lucio Palombini, ProfMD i, Gennaro Chiappetta, MD j, Gerardo Botti, MD j, Aldo Vecchione, ProfMD j, Rino Bellocco, ScD k, l

for the Italian Thyroid Cancer Study Group (ITCSG)

a Department of Pathology, St Andrea University Hospital, Rome, Italy 
b Cellular and Molecular Tumour Pathology Laboratory, Karolinska Cancer Centre, Karolinska Hospital, Stockholm, Sweden 
c Department of Pathology, St Giovanni Battista Hospital, Turin, Italy 
d Department of Endocrinology, Azienda University Hospital, St Luigi, Orbassano, University of Turin, Italy 
e Department of Endocrinology, University La Sapienza of Rome, Italy 
f St Peter Hospital Research Centre, Fatebenefratelli Association for Research (AFaR), Italy 
g Department of Pathology, Veneto Institute of Oncology, Istituto Oncologico Veneto (IOV-IRCCS), Italy 
h Department of Endocrinology, University of Padua, Padua, Italy 
i Departments of Pathology and Cytology, University Federico II, Naples, Italy 
j Departments of Pathology and Endocrinology, National Cancer Institute, Fondazione Pascale, Naples, Italy 
k Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden 
l Department of Statistics, University of Milano Bicocca, Milan, Italy 

* Correspondence to: Dr Armando Bartolazzi, Department of Pathology, St Andrea Hospital, Via di Grottarossa 1035, 00189 Rome, Italy

Summary

Background

In the USA, about 30200 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.

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