Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms

AIMS: To determine whether galectin-3 is a sensitive indicator of thyroid malignancy. It has been suggested as a potential marker for differentiating thyroid carcinoma from benign or non-neoplastic lesions in preoperative fine-needle aspirates (FNAs). METHODS: Galectin-3 protein expression was assessed by immunohistochemistry in formalin-fixed thyroid tissues from 124 patients with histological diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 19), follicular adenoma (n = 32) and dominant nodules of multinodular goitre (n = 35). Expression of galectin-3 was also assessed by Western blotting in 24 fresh thyroid tissues. RESULTS: Galectin-3 expression was observed in the majority of carcinomas (papillary 92%; follicular 74%). However, a large proportion of follicular adenomas (72%) and multinodular goitres (57%) also expressed galectin-3. In addition, galectin-3 expression was observed in epithelial cells of normal thyroid tissue and Hashimoto's thyroiditis. Galectin-3 immunopositivity was significantly greater in papillary carcinomas than in dominant nodules or follicular adenomas (P < 0.0001, P = 0.0005, respectively). However, galectin-3 expression was no greater in follicular carcinomas than in follicular adenomas (P = 0.8735). Western blotting analysis confirmed both the specificity of the antiserum and expression of galectin-3 in multinodular goitres, follicular adenomas/carcinomas and papillary carcinomas. CONCLUSION: The data demonstrate that galectin-3 is not a reliable immunohistochemical marker to distinguish benign from malignant thyroid follicular lesions.     

Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules

AIMS: The immunohistochemical expression of cytokeratin 19 (CK 19) and galectin-3 was evaluated in 69 thyroid lesions to assess their potential as markers in the diagnosis and classification of thyroid malignancy. The following were studied: 26 cases of papillary carcinoma, 12 of follicular carcinoma, 20 follicular adenomas, two medullary carcinomas, one anaplastic carcinoma and eight multinodular goitres. METHODS AND RESULTS: Formalin-fixed paraffin-embedded thyroid tissues were stained immunohistochemically for both CK 19 and galectin-3. CK 19 expression was found in all 26 papillary carcinomas, five of 12 follicular carcinomas, two of two medullary carcinomas and one case of anaplastic carcinoma. Only five of 20 follicular adenomas were positive for CK 19, and this was in a focal distribution. Two of eight multinodular goitres stained focally positive. Galectin-3 expression was found in 22 of 26 papillary carcinomas, 12 of 12 follicular carcinomas and one of two cases of medullary carcinoma. Only two of 20 follicular adenomas were positive. Three of eight multinodular goitres showed focal galectin-3 expression. CONCLUSIONS: Our findings suggest that the immunohistochemical localization of CK 19 and of galectin-3 is a useful adjunct to the histopathological diagnosis of a solitary thyroid lesion. The expression of CK 19 favours a diagnosis of papillary carcinoma in all its variant patterns. Galectin-3 may serve as a marker for the recognition of follicular carcinoma, particularly the minimally invasive form.     

The expression profiles of the galectin gene family in primary and metastatic papillary thyroid carcinoma with particular emphasis on galectin-1 and galectin-3 expression

IntroductionGalectin family members have been demonstrated to be abnormally expressed in cancer at the protein and mRNA level. This study investigated the levels of galectin proteins and mRNA expression in a large cohort of patients with papillary thyroid carcinoma and matched lymph node metastases with particular emphasis on galectin-1 and galectin-3.MethodsmRNA expression of galectin family members (1, 2, 3, 4, 7, 8, 9, 10 and 12) were analysed by real-time polymerase chain reaction in 65 papillary thyroid carcinomas, 30 matched lymph nodes with metastatic papillary thyroid carcinoma and 5 non-cancer thyroid tissues. Galectin-1 and 3 protein expression was determined by immunohistochemistry in these samples.ResultsSignificant expression differences in all tested galectin family members (1, 2, 3, 4, 7, 8, 9, 10 and 12) were noted for mRNA in papillary thyroid carcinomas, with and without lymph node metastasis. Galectin-1 protein was more strongly expressed than galectin-3 protein in papillary thyroid carcinoma. Galectin-1 protein was found to be overexpressed in 32% of primary papillary thyroid carcinomas. A majority of lymph nodes with metastatic papillary thyroid carcinoma (53%) had significantly increased expression of galectin-1 protein, as did 47% of primaries with metastases. Galectin-1 mRNA levels were decreased in the vast majority (94%) of primary thyroid carcinomas that did not have metastases present. Galectin-3 protein levels were noted to be overexpressed in 15% of primary papillary thyroid carcinomas. In primary papillary thyroid carcinoma with lymph node metastases, 32% had over expression of galectin-3 protein. Overexpression of galectin-3 mRNA was noted in 58% of papillary thyroid carcinomas and 64% of lymph nodes bearing metastatic papillary thyroid carcinoma. Also, primary papillary thyroid carcinoma with lymph node metastases had significantly higher expression of galectin-3 mRNA compared to those without lymph node metastases.ConclusionGalectin family members show altered expression at the mRNA level in papillary thyroid cancers. Overexpression of galectin-1 and 3 proteins were noted in papillary thyroid carcinoma with lymph node metastases. The results presented here demonstrated that galectin-1 and galectin-3 expression have important roles in clinical progression of papillary thyroid carcinoma.     

Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms

Galectin-3 is a 31kD beta-galactoside binding lectin, which is known to be expressed in various neoplasms including thyroid tumors. This study was conducted to study the role of galectin-3 in differentiating benign from malignant thyroid nodules onfine needle aspirates (FNAC). Galectin-3 immuocytochemistry was performed in 70 cases with adequate smears. The cytology diagnosis of these cases was: papillary carcinoma (25), follicular neoplasm (16), adenomatous goiter (20), hyperplastic nodule (5), medullary carcinoma (5) and anaplastic carcinoma (1). Galectin-3 positivity was seen in 80% of papillary carcinomas, 37.5% offollicular neoplasms and in 60% of benign nodules. The single case of anaplastic carcinoma was positive but all the cases of medullary carcinoma were negativefor galectin-3. Three of thefollicular neoplasms that were diagnosed on histology as carcinoma were positive on cytology and one case offollicular adenoma was also positive. Our study shows that galectin-3 is strongly expressed in smears of papillary carcinoma. However, since it is also expressed in a variety of benign lesions, its role as a pre-surgical markerfor differentiating benignfrom malignant thyroid nodules is limited.     

Galectin-3 Expression in Tumor Progression and Metastasis of Papillary Thyroid Carcinoma

Galectin-3 plays important roles in cell adhesion, cell proliferation, apoptosis, neoplastic transformation, and metastasis. Galectin-3 expression has been evaluated in various malignant neoplasms to determine its effectiveness in differential diagnosis from benign lesions and its effects on carcinogenesis. There are few and somewhat controversial results regarding its changes through cancer progression in thyroid malignancies. We studied the presence of galectin-3 expression immunohistochemically and its relation with tumor invasiveness and lymph node metastasis in 89 cases of papillary carcinoma of the thyroid. Galectin overexpression was less frequent in cases with lymph node metastases compared with cases without lymph node metastasis (P = 0.001). Metastatic foci in lymph nodes showed a lower degree of galectin-3 overexpression than their primary lesions (P = 0.001). Degree of galectin-3 overexpression was also lower in larger tumors (P = 0.009). Additionally, a decreased level of galectin-3 overexpression was observed at the invasive edges of the tumors (P = 0.001). Galectin-3 overexpression is more profound in early stages of papillary carcinoma, and its expression intensity decreases during tumor progression. This finding is consistent with roles for galectin-3 in cell adhesion to other tumor cells and the matrix.     

Desmoplastic stromal reaction in papillary thyroid microcarcinoma

Koperek O, Asari R, Niederle B & Kaserer K
(2011) Histopathology  58 , 919–924
Desmoplastic stromal reaction in papillary thyroid microcarcinoma Aims: To evaluate the value of a desmoplastic stromal reaction (desmoplasia) as an indicator of metastasis in papillary thyroid microcarcinoma. Methods and results: One hundred and nine cases of papillary thyroid microcarcinoma from the pathological archive of the Medical University of Vienna, Austria were analysed for the presence of desmoplasia in relation to other morphological and clinicopathological parameters. Eighty‐one of 109 papillary microcarcinomas showed a desmoplastic stromal reaction. The desmoplasia was significantly associated with lymph node metastases (P = 0.001) and tumour diameter (P < 0.001). In addition, ‘invasive parameters’, such as peritumoral and vascular invasion, were associated with the presence of a desmoplastic stromal reaction (P < 0.001 and P = 0.006, respectively), and all pT3b tumours according to the UICC classification of 2002 (i.e. with perithyroidal infiltration) showed desmoplasia. Of all morphological parameters, the best indicator of lymph node metastasis was tumour calcification (P < 0.001). Conclusions: Our data indicate that a desmoplastic stromal reaction seems to be an indicator of invasive behaviour of papillary thyroid microcarcinomas significantly associated with lymph node metastases. Papillary microtumours without signs of invasion, e.g. desmoplasia, should not be regarded as invasive carcinoma, as they are more likely to be thyroidal intraepithelial neoplasias.     

Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions

CONTEXT: The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions. DESIGN: We studied the immunohistochemical expression pattern of galectin-3 in a variety of follicular-derived thyroid lesions (13 benign and 62 malignant), including Hürthle cell and follicular carcinoma, papillary carcinomas and variants, and anaplastic and poorly differentiated carcinomas. RESULTS: Immunoreactivity was strongest in papillary thyroid carcinomas, whereas staining was less intense in Hürthle cell and anaplastic carcinomas, and even weaker in the follicular variant of papillary thyroid carcinoma. Staining was absent or weak in the 3 follicular thyroid carcinomas and was negative in both insular carcinomas. In several tumors, staining was stronger at the advancing invasive edge of the lesion than in the central portion of the tumor. Galectin-3 was also expressed focally and weakly in reactive follicular epithelium and entrapped follicles in chronic lymphocytic thyroiditis. A variety of thyroid lesions showed prominent endogenous, biotin-like activity, which could cause flaws in interpretation if a biotin-detection system were used. CONCLUSION: We conclude that galectin-3 immunostaining, when used in biotin-free detection systems, may be useful as an adjunct to distinguish benign from malignant thyroid lesions.     

Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation

Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important role in cell-cell adhesion and in cell-matrix interaction. We have examined the expression of galectin-3 in normal, adenomatous, and malignant thyroid tissues and also in metastatic lesions. Galectin-3 was rarely expressed in normal thyroid tissue but was abundant in the cytoplasm of the neoplastic lesions. Among neoplastic lesions, galectin-3 was expressed to a greater extent in follicular carcinomas than in follicular adenomas and was present in greater amounts in papillary carcinomas than in follicular adenomas or carcinomas. Primary lesions of papillary carcinoma with metastasis contained significantly higher concentrations of galectin-3 than tumors of this type without metastases. However, the expression of galectin-3 was significantly decreased in metastatic lesions in the lymph nodes compared with their primary lesions. From these results, we assumed that galectin-3 works in different ways at different stages of thyroid neoplasm proliferation. Among primary tumors, galectin-3 expression is significantly different in 3 histological types. However, the continuity of progression among these tumors is not yet proven. In later stages, decreased expression of galectin-3 may aid the release of cancer cells from the primary lesions for invasion and metastasis.     

p53, ki-67, galectin-3, HBME-1, 34βE12和CK19在甲状腺乳头状癌中的表达及临床病理意义

 摘要：目的：探讨p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19在甲状腺乳头状癌中的表达及临床病理意义。方法：采用免疫组化检测43例甲状腺乳头状癌、37例结节性甲状腺肿、33例甲状腺腺瘤和17例桥本甲状腺炎中p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19的表达。结果：p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19在甲状腺乳头状癌中的阳性表达例数分别为88.37%、79.07%、88.37%、93.02%、86.05%、95.35%;6种蛋白在甲状腺乳头状癌与结节性甲状腺肿、甲状腺腺瘤和桥本甲状腺炎中的阳性表达率相比较差异均有统计学意义（P<0.01）。结论：联合检测p53, ki-67, galectin-3, HBME-1, 34βE12和CK-19在甲状腺乳头状癌与良性病变的诊断和鉴别诊断中具有重要的价值。     

Galectin-3 and carcinoembryonic antigen expression in medullary thyroid carcinoma: possible relation to tumour progression

AIMS: Galectin-3 is a beta-galactoside binding protein involved in multiple biological processes through interactions with complementary glycoconjugates. We analysed the expression and coexpression of galectin-3 and carcinoembryonic antigen (CEA), one of the putative galectin-3 ligands, in medullary thyroid carcinoma (MTC). METHODS AND RESULTS: An immunohistochemical study using monoclonal antibodies was performed on paraffin sections of 20 cases of sporadic MTC comprising 10 cases without and 10 cases with lymph node metastases at the time of surgery. CEA expression was found in all tumours, distributed predominantly in the cytoplasm and occasionally at the cell surface. In the majority of cases (18/20) moderate to strong intensity of staining was found in most of the cells. Positive cytoplasmic staining for galectin-3 was found in 16/20 cases, but varied in intensity and distribution from weak/focal (7/16) to moderate (7/16) or strong (2/16). More intense staining for galectin-3 was mainly associated with MTC cases involving lymph node metastases. Eight out of these 10 cases showed moderate to strong galectin-3 expression concomitant with CEA expression throughout the tumour tissue. CONCLUSIONS: These findings suggest that galectin-3 might play a role in the pathobiology of MTC. Simultaneous expression of galectin-3 and CEA in the same tumour cells at an advanced stage of MTC indicates the possibility of their autocrine cooperation during tumour progression.     

Expression of galectin-3 in normal and malignant thyroid tissue by quantitative PCR and immunohistochemistry.

Galectin-3 has been extensively studied as an immunohistochemical marker of thyroid malignancy, and a high diagnostic accuracy has been reported even for difficult pathological diagnoses, such as minimal invasive follicular carcinoma. We consequently hypothesized that the quantitative analysis of galectin-3 mRNA rather than the more observer-dependent immunohistological determination might enhance the diagnostic workup of ambiguous thyroid lesions. In the present study, we set out to validate this approach by analyzing concomitantly the expression and production of galectin-3 in benign and malignant thyroid tumors by means of quantitative PCR and immunohistochemistry. Twenty-eight benign and 31 malignant thyroid samples were quantified by real-time PCR for the mRNA levels of galectin-3 and thyroglobulin. Galectin-3 protein expression was examined by immunohistochemistry in 13 benign and 14 malignant thyroid samples. There was a significant increase in galectin-3 at both the mRNA (12/20) and protein levels in papillary cancer (8/8), although the mRNA values overlapped partly with benign lesions. Surprisingly, only a focal and discrete galectin-3 immunoreactivity was seen in follicular cancer (1/5); no augmentation of the mRNA was found. The expression of the thyroid-specific gene thyroglobulin was highly variable in benign and malignant thyroid tissue. These results suggest that the quantitative measurement of galactin-3 mRNA is unlikely to be clinically useful and underscore the need for searching for novel markers for thyroid malignancies.     

Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia

AIMS: The distribution of galectin-3, a widely recognized marker of well-differentiated thyroid carcinoma, was investigated in 95 thyroid lesions including nodules with foci of cytoarchitectural atypia. METHODS AND RESULTS: Twenty-eight papillary carcinomas, five follicular carcinomas, one Hurthle cell carcinoma, three poorly differentiated carcinomas, one anaplastic carcinoma, 25 nodular hyperplasias and 27 follicular adenomas, including nodules with atypical features, three neoplasms of undetermined malignant potential and two thyroiditis cases were examined. By immunohistochemistry, galectin-3 was consistently found in carcinomas; otherwise benign nodules exhibited galectin-3-positive clusters of cells with poorly developed features of differentiated carcinoma (mainly of papillary type) such as nuclear chromatin clearing, nuclear clefting, pseudoinclusions, which, in each case, were not histologically sufficient to warrant a definitive diagnosis of malignancy. In other nodules galectin-3 staining was negative. The latter were either clearly benign or showed constantly a minor degree of chromatin clearing and of other atypical features when compared with galectin-3-positive cases. CONCLUSIONS: Galectin-3, a reliable marker of differentiated thyroid carcinoma as confirmed in our series of malignant neoplasms, appears expressed in nodules with an overall benign appearance but with focal areas suspicious for malignancy. The significance of such findings needs to be further investigated.     

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin-fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.     

Immunohistochemical expression of HBME-1 and galectin-3 in the differential diagnosis of follicular-derived thyroid nodules

BackgroundThyroid nodules are common among adults with only a small percentage being malignant and histologically mimic benign nodules. Accurate diagnosis of these thyroid nodules is critical for the proper clinical management. The determination of malignancy in follicular patterned thyroid lesions is based on postoperative histological findings. Therefore, affected patients are referred for surgery, although only 10% will have a final diagnosis of malignancy. The aim of this study was to investigate the ability of two immunohistochemical (IHC) markers; galectin-3 and Hector Battifora mesothelial-1 (HBME-1) individually or in combination, to distinguish between benign (non-neoplastic and neoplastic) and malignant (follicular and papillary carcinomas) thyroid lesions removed by surgical resection.MethodsWe investigated the immunoexpression of galectin-3 and HBME-1 in 50 cases of benign and malignant thyroid nodules. The benign group included 13 cases of thyroid nodular goiter (NG) and 9 cases of follicular adenoma (FA). The malignant group included 5 cases of follicular thyroid carcinomas (FC), 18 cases of classic papillary thyroid carcinoma and 5 cases of follicular variant papillary carcinoma (FVPC).ResultsThe staining results showed that malignant tumors expressed galectin-3 and HBME-1 significantly more than benign nodules. The sensitivity of these markers for the distinction between benign and malignant lesions ranged from 89.3% to 92.9%. Co-expression of galectin-3 and HBME-1 was seen in 82.1% of carcinomas, but in none of the benign nodules. Immunoexpression was usually diffuse in malignant tumors, and focal in the benign lesions.ConclusionOur findings indicate that these immunohistochemical markers are significantly more expressed in malignant tumors compared to benign lesions and may be of additional diagnostic value when combined with routine histology. Galectin-3 has higher sensitivity and specificity of immunoexpression in thyroid malignancy than HBME-1, and the combined use of galectin-3 and HBME-1 can increase the specificity of immunoexpression in malignant tumors.     

Apoptosis and proliferation related molecules (Bcl-2, Bax, p53, PCNA) in papillary microcarcinoma versus papillary carcinoma of the thyroid

AIM: To gain a better insight into the differences in biological behaviour between papillary microcarcinoma (PMC) and clinically evident papillary thyroid carcinoma (PTC). METHODS: Immunohistochemical analysis of apoptosis related molecules (Bcl-2, Bax, p53) and proliferation related marker (PCNA) in 39 archival cases of PMC and 46 cases of PTC. RESULTS: Bcl-2 and Bax were expressed in most PMCs and PTCs. The average Bcl-2 staining score did not differ significantly between PMCs and PTCs (p > 0.05), but the average Bax score was significantly lower in PMCs (p < 0.05). The Bcl-2/Bax ratio was significantly higher in PMCs than in PTCs (p < 0.05). The expression of p53 was similar in PMCs and PTCs, without a correlation with clinical data, but was associated with high Bax expression (p < 0.05) in these cases in both groups. Non-malignant tissue expressed only Bcl-2, but not p53 or Bax. PCNA expression was significantly lower (p < 0.05) in PMC than in PTC and positively correlated with tumour size (p < 0.05). CONCLUSIONS: The higher Bcl-2/Bax ratio and lower proliferative activity in PMC suggest differences from PTC in the balance between apoptosis and proliferation. However, the presence of p53 and Bax in PMC indicates malignant potential, and thus PMC should be treated with caution.     

Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy

Aims : To investigate the usefulness of immunohistochemical expression and immunolocalization of a panel of thyroid malignancy markers including HBME-1, cytokeratin (CK) 19 and galectin-3.
Methods and results : We evaluated 170 thyroid lesions including 148 neoplastic lesions [84 papillary carcinomas (PC), 38 follicular carcinomas (FC), 18 follicular adenomas, one hyalinizing trabecular tumour, five medullary carcinomas, two anaplastic carcinomas] and 22 non-neoplastic lesions (12 adenomatous nodules and 10 Hashimoto's thyroiditis). HBME-1, galectin-3 and CK19 were expressed in 94%, 72.6%, 72.6% of PCs and in 63%, 21%, 21% of FCs. The three markers were mostly negative in all normal tissues. Although the most helpful marker in terms of sensitivity and specificity for the follicular variant of PC and for FC diagnosis was HBME-1, when we consider the differentiation between cases of follicular variant of papillary carcinoma (FVPC) and FC or adenoma, in terms of percentage of positive cells, galectin-3 and CK19 were more relevant.
Conclusions : HBME-1 is the most sensitive marker for thyroid malignancy but the three markers may be useful in specific cases. This panel of markers is useful to differentiate the follicular patterned lesions, with special reference to the FVPC.     

Thyroid peroxidase and galectin-3 immunostaining in differentiated thyroid carcinoma with clinicopathologic correlation

Thyroperoxidase and galectin-3 have been reported as useful immunohistochemical markers of thyroid malignancy. In this study, we evaluated the relationship between immunohistochemical staining results for these markers and clinicopathologic features of patients with differentiated thyroid cancer. A total of 193 archival thyroid samples including 28 follicular adenomas, 18 follicular carcinomas, and 147 papillary carcinomas with 114 adjacent thyroid tissues were analyzed by immunohistochemistry. Thyroperoxidase was underexpressed (<50% stained thyrocytes), and galectin-3 was expressed (>5% stained thyrocytes) in most carcinomas. The sensitivity for diagnosis of differentiated thyroid carcinoma was 86.1% for thyroperoxidase and 82.4% for galectin-3, whereas the combination of both markers increased the sensitivity up to 94.5%. Thus, the combination of thyroperoxidase and galectin-3 immunohistochemistry may help to ascertain the malignant nature of the lesion. Furthermore, tumor size, nodal involvement, extrathyroidal invasion, and high tumor-node-metastasis stage in patients with papillary carcinoma were related to thyroperoxidase absence and high galectin-3 expression in most cases (P < .05). In patients with follicular carcinoma, the extent of invasiveness was associated with galectin-3 positivity. Thus, expression of these markers is related to more or less aggressive biological behavior of differentiated thyroid carcinomas. Although thyroperoxidase presence may indicate favorable prognosis of papillary cancer, expression of galectin-3 illustrates the potential importance of this protein in the pathogenesis and/or progression of differentiated thyroid carcinomas.     

Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications.

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas.     

Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma

The accurate diagnosis of differentiated thyroid tumors is very important for clinical management of patients. The histopathological distinction between some types of differentiated thyroid tumors can be very difficult even for experienced pathologists. We used immunohistochemical markers from published data obtained from DNA expression profiling, tissue microarray analysis, and immunohistochemistry to analyze a series of 157 thyroid tumors and 5 normal thyroids. These analyses showed that several antibodies were useful in distinguishing follicular adenomas from follicular variant of papillary thyroid carcinomas including HBME-1, CITED 1, galectin-3, cytokeratin 19, and S100A4 (p<0.0001). A combination of markers consisting of a panel of HBME-1, galectin-3, and CK19 or a panel of HBME-1, CITED1, and galectin-3 was usually most effective in distinguishing follicular adenoma from follicular variant of papillary thyroid carcinoma. Because individual tumors may not express some of these markers, the use of a panel of antibodies is recommended. These results indicate that some individual antibodies or a panel of antibodies combined with histopathological analysis can be useful in separating follicular adenoma (FA) from follicular variant of papillary thyroid carcinoma (FVPTC).