Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors

Abstract

The diagnosis of thyroid tumors is critical for clinical management; however, tumors with follicular architecture often present problems. We evaluated the diagnostic use of the protein expression of four genes that were found to be upregulated in papillary thyroid carcinoma compared to normal thyroid (LGALS3, FN1, CITED1 and KRT19), and of the mesothelial cell surface protein recognized by monoclonal antibody HBME1 in thyroid tumors. Tissues from 85 carcinomas (67 papillary, six follicular, eight Hü rthle cell and four anaplastic) and 21 adenomas were evaluated by immunohistochemistry for the expression of these gene protein products, for example, galectin-3 (GAL3), fibronectin-1 (FN1), CITED1, cytokeratin-19 (CK19) and HBME1. Non-neoplastic thyroids (29 adenomatous and 14 thyrotoxic hyperplasia, and 59 normal) were also studied. The expression of all five proteins was significantly associated with malignancy, and highly specific (Z90%) for carcinoma compared to adenoma. GAL3, FN1 and/or HBME1 expression was seen in 100% of carcinomas (85/85) and in 24% of adenomas (5/21). Coexpression of multiple proteins was seen in 95% of carcinomas and only 5% of adenomas (Po0.0001). Coexpression of FN1 and GAL3 (FN1 þ GAL3 þ , 70/85) or FN1 and HBME1 (FN1 þ HBME1 þ , 53/85) was restricted to carcinomas, while their concurrent absence (FN1ÀGAL3À or FN1ÀHBME1À, 18/21 adenoma) was highly specific (96%) for benign lesions. Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 (n ¼ 16), CK19 (n ¼ 9) and CITED1 (n ¼ 7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas. An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors.

Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV

“…Thyrotoxic hyperplasia was consistently negative (Rossi et al, 2006) whereas nodular goitres were positive in up to 17% of cases (Ito et al, 2005). Significant reactions were also reported in 25% of thyroiditis (Prasad et al, 2005), 5 -10% of benign follicular tumours devoid of atypical features, and up to 65% with LNFPTC or Hürthle cell features (Mai et al, 2002;Papotti et al, 2005;Prasad et al, 2005;Scognamiglio et al, 2006). The fact that specificity in our study was in the lower range may be due to a high proportion of atypical or Hürthle cell tumours and absence of hyper-functional nodules.…”

“…However, overall results obtained on fresh tissue, including our study, and cell blocks are rather concordant. The sensitivity of HBME-1 staining was excellent (490%) for classical PC (van Hoeven et al, 1998;Ito et al, 2005;Rossi et al, 2005), disappointing for PCFV, and poor (o65%) for follicular and undifferentiated cancers (Cheung et al, 2001;Mai et al, 2002;Ito et al, 2005;Prasad et al, 2005;Saggiorato et al, 2005). The reported specificity of HBME-1 staining ranged from 70% to more than 90% (Cheung et al, 2001;Prasad et al, 2005;Saggiorato et al, 2005).…”

“…Hector Battifora mesothelial antigen-1 immunohistochemistry is usually negative in benign thyroid lesions and positive on carcinomas. Most studies using HBME-1 for diagnosis of thyroid tumours have been performed on tissue samples (Mai et al, 2002;Ito et al, 2005;Papotti et al, 2005;Prasad et al, 2005). A few studies using FNA products have been carried out on cell blocks or thin layers (Sack et al, 1997;van Hoeven et al, 1998;Rossi et al, 2005;Saggiorato et al, 2005).…”

CITED1 homozygous null mice display aberrant pubertal mammary ductal morphogenesis

“…It was subsequently shown to function as a transcriptional coregulator of both the estrogen receptor and SMAD4 in a manner dependent on either estrogen receptor ligand binding or TGFb induced SMAD dimerization and its interaction with the CBP/p300 transcriptional coactivator Yahata et al, 2000). Most recently, CITED1 has been defined as a marker for the differential diagnosis of papillary thyroid carcinoma (Aldred et al, 2004;Prasad et al, 2004;Prasad et al, 2005).…”

Expression of Matrix Metalloproteinase-2, but not Caspase-3, Facilitates Distinction between Benign and Malignant Thyroid Follicular Neoplasms

“…Prasad et al reported that a panel consisting of galectin-3, fibronectin-1 and HBME-1 may enhance the sensitivity and specificity for diagnosis of FTC versus FTA ( Prasad ML, et al 2005). Some studies have suggested trefoil factor 3 (TFF3) as a useful biomarker at the RNA level in thyroid cancer, and this gene was listed as 1 of 12 (of a total of 1795 genes) to have the most clinical promise (based on results of the array analysis) for the preoperative thyroid diagnosis (Griffith et al, 2006).…”