title: Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) immunoexpression in follicular-patterned lesions of the thyroid gland.
abstract: Neutrophil gelatinase-associated lipocalin (NGAL) is a protein which participates in iron trafficking and which is involved in cancerogenesis and cancer progression. Since its over-expression has been documented in thyroid malignancies in comparison to thyroid normal gland, in the present study, we aimed to determine whether the evaluation of NGAL immunoexpression may be of help in the differential diagnosis of follicular-patterned thyroid lesions. Our additional aim was to test the possible interference of endogenous biotin on the immunohistochemical findings. Thus, all the immunohistochemical procedures, carried out with labeled streptavidin biotin method, were doubly performed, with or without the preliminary inhibition of endogenous biotin. No NGAL staining was found in the normal thyroid gland nor in the nodular colloid goiters or in Hashimoto's thyroiditis. NGAL expression appeared to be significantly more frequent in the malignant tumors in comparison to benign ones (P < 0.000001). Even more, NGAL expression appeared to be specific (specificity 93%) for carcinoma and represented a sensitive method (sensitivity 84%), with high negative (88%) and positive (94%) predictive values, as well as high diagnostic accuracy (88%), in the identification of follicular-patterned thyroid malignant tumors. The specificity, positive predictive value and diagnostic accuracy lowered when biotin was not preliminary inhibited, due to the presence of false positives among benign Hürthle cell tumors. In conclusion, the immunohistochemical detection of NGAL may be helpful in the differential diagnosis between malignant and benign follicular-patterned lesions of the thyroid. The use of biotin free system or the preliminary biotin inhibition is warranted for the detection of NGAL in thyroid samples, especially when dealing with Hürthle cell tumors.
authors.affiliation: Department of Human Pathology, University of Messina, Messina, Italy. vbarresi@unime.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Barresi
authors.forename: Enrica
authors.initials: E
authors.lastname: Vitarelli
authors.forename: Luca
authors.initials: L
authors.lastname: Reggiani Bonetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tuccari
authors.forename: Gaetano
authors.initials: G
authors.lastname: Barresi
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D012680:Sensitivity and Specificity; D013959:Thyroid Diseases / Q000175:diagnosis* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins