Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential

Abstract

Well-differentiated encapsulated tumors of the thyroid gland with a follicular architecture may cause diagnostic difficulties. Questionable vascular or capsular penetration may raise the possibility of a follicular carcinoma, while focal nuclear clearing and grooves may suggest a diagnosis of papillary carcinoma. A proposal has recently been made to designate cases showing suggestive but not conclusive morphological evidence of malignancy along these lines as well-differentiated or follicular tumors of uncertain malignant potential. The aim of the present study was to investigate the expression and diagnostic role in well-differentiated or follicular tumors of uncertain malignant potential of Galectin-3 and HBME-1, two malignancy-related markers. A total of 21 tumors fulfilling the criteria of well-differentiated or follicular tumors of uncertain malignant potential were collected from two institutions, including eight cases with questionable vascular and/or capsular invasion and 13 cases with some degree of nuclear changes in the form of clearing, grooves, and/or pseudoinclusions. Tumors in the first group expressed HBME-1 and Galectin-3 focally (less than 25% of tumor cells) in 5/8 and 3/8 cases, respectively, with 62.5% of cases reacting for at least one marker. Cases in the second category expressed HBME-1 and Galectin-3 in 9/13 and 10/13 cases, respectively, with 92.3% of cases having at least one marker expressed. These findings indicate that HBME-1 and Galectin-3 are heterogeneously distributed in these borderline tumors, but that a strong and diffuse expression of HBME-1 and to a lower extent of Galectin-3 was preferentially observed in the group characterized by nuclear changes which were similar but less developed than those of conventional papillary carcinoma. The relationship found between the markers investigated and these nuclear changes suggests that the tumors containing them are pathogenetically linked to papillary carcinomas.

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.…”

“…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).…”

Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology

“…The PPV was 78.4% (492% if galectin-3-positive follicular proliferations UMP are considered as early transformed lesions or 'thyroid cancer precursor lesions') (Bartolazzi et al, 2001;Papotti et al, 2005), whereas the NPV was 98.6%. Diagnostic accuracy assessed in this study was 95.3%, and frequency 14.1.…”

“…Galectin-3 expression was also detected in three out of six histologically confirmed follicular adenomas. Two of these lesions were finally diagnosed as 'follicular proliferations with undefined malignant potential (UMP) (Rosai et al, 1992;Papotti et al, 2005) because evidence of capsular impingement of the neoplastic cells, without clear aspects of invasion, was histologically demonstrated after evaluation of multiple tissue sections. In one instance, LNAB material showed galectin-3-positive atypical cells.…”

“…HBME1, CK19, CD26/DPPIV, TPO and c-met have also been reported to be useful markers for improving the preoperative characterisation of thyroid nodules (De Micco et al, 1994Ruco et al, 2001;Aratake et al, 2002;Rosai, 2003;Maruta et al, 2004;Mechanick, 2004;Weber et al, 2004;Papotti et al, 2005;Prasad et al, 2005;Saggiorato et al, 2005;de Matos et al, 2005). Among the aforementioned molecules, TPO is the largest preoperatively investigated tumour marker with a high overall accuracy (De Micco et al, 1994Christensen et al, 2000;Weber et al, 2004).…”