Combined immunostaining with galectin-3, fibronectin-1, CITED-1, Hector Battifora mesothelial-1, cytokeratin-19, peroxisome proliferator-activated receptor-{gamma}, and sodium/iodide symporter antibodies for the differential diagnosis of non-medullary thyroid carcinoma.
OBJECTIVE
The microscopic distinction between benign and malignant thyroid lesions in clinical practice is still largely based on conventional histology. This study was performed to evaluate the diagnostic value of galectin-3 (Gal-3), Hector Battifora mesothelial-1 (HBME-1), cytokeratin (CK)-19, CBP P300-interacting transactivator with glutamic acid E- and aspartic acid D-rich C-terminal domain (CITED-1), fibronectin (FN)-1, peroxisome proliferator-activated receptor (PPAR)-gamma, and intracellular sodium/iodide symporter (iNIS) immunostaining in a large panel of thyroid neoplasms. Our study differed from earlier ones with regard to the identification of optimal semiquantitative cut-off levels using receiver operator curve (ROC) analysis and hierarchical cluster analysis.


METHODS
We used tissue arrays containing 177 thyroid tissues: 100 benign tissues (including normal thyroid, Graves disease, multinodular goiter, and follicular adenoma (FA)) and 77 thyroid carcinomas (including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, and follicular variant of PTC (FVPTC)). Antibody staining was scored semiquantitatively based on the ROC analyses and with hierarchical cluster analysis.


RESULTS
In general, we found overexpression of FN-1, CITED-1, Gal-3, CK-19, HBME-1, and iNIS in malignant thyroid lesions. Gal-3, FN-1, and iNIS had the highest accuracy in the differential diagnosis of follicular lesions. A panel of Gal-3, FN-1, and iNIS, identified by hierarchical cluster analysis, had a 98% accuracy to differentiate between FA and malignant thyroid lesions. In addition, HBME-1 was found to be useful in the differentiation between FA and FVPTC (accuracy 88%).


CONCLUSIONS
We conclude that identifying optimal antibody panels with cluster analysis increases the diagnostic value in the differential diagnosis of thyroid neoplasms, the combination of FN-1, Gal-3, and iNIS having the best accuracy (98%).
Liu
Ying Y
YY
Department of Endocrinology, C4-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Morreau
Hans
H
Kievit
Job
J
Romijn
Johannes A
JA
Carrasco
Nancy
N
Smit
Johannes W
JW
D018263:Adenocarcinoma, Follicular / Q000378:metabolism* / Q000473:pathology*; D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism; D037502:Galectin 3 / Q000276:immunology / Q000378:metabolism; D006044:Goiter, Nodular / Q000378:metabolism / Q000473:pathology; D006111:Graves Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D047495:PPAR gamma / Q000276:immunology / Q000378:metabolism; D012372:ROC Curve; D027981:Symporters / Q000276:immunology / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D000099209:Sodium-Iodide Symporters; D000951:Antigens, Neoplasm
D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D005353:Fibronectins; D037502:Galectin 3; D053539:Keratin-19; D009687:Nuclear Proteins; D047495:PPAR gamma; D027981:Symporters; D015534:Trans-Activators; D014157:Transcription Factors; D000099209:Sodium-Iodide Symporters; C512688:CITED1 protein, human; C432845:HBME-1 antigen; D000951:Antigens, Neoplasm