甲状腺乳头状癌中CK19、Galectin-3、HBME-1和TPO的表达及意义

目的 探讨CK19、Galectin-3、HBME-1和TPO在甲状腺良恶性病变中的表达及联合应用在甲状腺乳头状癌鉴别诊断中的价值.方法 采用免疫组化EnVision法检测68例甲状腺乳头状癌、31例甲状腺腺瘤、19例结节性甲状腺肿和15例桥本甲状腺炎中CK19、Galectin-3、HBME-1和TPO的表达.结果 在甲状腺乳头状癌中CK19、Galectin-3和HBME-1的阳性表达率分别为98.5%、98.5%、80.9%,TPO的阴性表达率为89.7%;在甲状腺良性病变中CK19、Galectin-3和HBME-1阳性表达率分别是24.6%、21.5%、1.5%,TPO的阴性表达率是1.5%.CK19、Galectin-3、HBME-1和TPO在甲状腺乳头状癌与良性病变中的表达差异有显著性(P<0.001).联合应用四种抗体在鉴别甲状腺乳头状癌与良性病变时的敏感性、特异性、准确度分别为95.6%、98.5%、97%.结论 CK19、Galectin-3、HBME-1和TPO是诊断甲状腺乳头状癌的重要标志物.联合应用四种抗体在甲状腺乳头状癌与良性病变的鉴别诊断中具有重要价值.     

Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.     

HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma

The cytologic diagnosis of papillary thyroid carcinoma is straightforward in most instances. However, there are some mimics including goitrous nodules and Hurthle cell neoplasms. Many studies have shown the combination of HBME-1 and CK19 expression to be useful in reaching a correct histologic diagnosis on tissue sections. We aim to assess the value of these markers in the setting of cell blocks prepared from needle aspiration specimens. We performed immunohistochemical staining of HBME-1 and CK19 on cell block material from 22 thyroid nodules that also had follow-up histology. Both CK19 and HBME-1 were strongly positive in all nine cases of papillary thyroid carcinoma, the latter showing distinct luminal accentuation. In the non-papillary carcinomas, none showed positivity for both HBME-1 and CK19. Two of six Hurthle cell neoplasms were positive for CK19, however all were negative for HBME-1. One of nine goitrous nodules was strongly positive for HBME-1 with luminal/membranous staining, but this were negative for CK19. The sensitivity, specificity and positive predictive value of HBME-1 in distinguishing between papillary thyroid carcinoma and goitrous nodules/Hurthle cell neoplasms were found to be 100%, 92.9% and 0.9, respectively; and that of HBME-1 and CK19 combination was 100%, 100% and 1. We thus conclude that the combination of positive HBME-1 (luminal/membranous) and CK 19 (cytoplasmic) staining on cell blocks of thyroid cytologic specimens is highly discriminatory in the diagnostic workup for papillary thyroid carcinoma.     

Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections

An antiserum to carcinoembryonic antigen (CEA) and a monoclonal antibody to cytokeratin 19 (CK 19) were studied for their suitability as diagnostic reagents for the differential diagnosis of primary and secondary malignant epithelial tumours of the liver, on paraffin sections. With the antiserum to CEA, positive bile canalicular structures were found in 60 per cent of the hepatocellular carcinomas. All the cholangiocarcinomas and 66.6 per cent of the metastatic carcinomas were positive for CEA, without displaying a canalicular staining pattern. All the hepatocellular carcinomas were negative for CK 19. All the cholangiocellular carcinomas and the metastatic carcinomas were positive for CK 19. This staining profile may prove helpful in difficult diagnostic cases.     

甲状腺微小乳头状癌中Galectin-3、CK19、HBME-1和CD56的表达及意义

目的探讨结节性甲状腺肿合并甲状腺微小乳头状癌中Galectin-3、CK19、HBME-1及CD56的表达及意义。方法采用免疫组化SP法检测10例结节性甲状腺肿合并甲状腺微小乳头状癌中Galectin-3、CK19、HBME-1和CD56的表达水平。结果 Galectin-3、CK19和HBME-1在甲状腺微小乳头状癌中均呈中至强阳性表达,而在结节性甲状腺肿中主要呈阴性或弱阳性表达。然而在10例甲状腺微小乳头状癌中有8例CD56的表达均为阴性,2例呈轻度阳性着色;周围结节性甲状腺肿组织9例均呈中至强阳性表达,仅1例呈轻度阳性着色。结论 Galectin-3、CK19、HBME-1及CD56联合检测将进一步提高甲状腺微小乳头状癌的准确性。     

Diagnostic utility of cytokeratin 19 expression in multinodular goiter with papillary areas and papillary carcinoma of thyroid

The most common benign lesion of thyroid, multinodular goiter, may mimic papillary carcinoma if it contains papillary areas. Although it is usually not very difficult to distinguish between these benign and malignant lesions, some cases may be problematic in differential diagnosis. In these cases, we decided to use cytokeratin 19 (CK 19), which is shown to be effective in discriminating papillary carcinoma from follicular carcinoma of thyroid, and we also evaluated the immunoreactivity of CK19 in follicular adenomas. Twenty-five cases of multinodular goiter showing papillary formations, 25 cases of papillary thyroid carcinoma, and 15 cases of follicular adenoma were selected from archives of our institution. Immunohistochemical staining for CK19 was performed on deparaffinized sections. Diffuse and intense CK19 positivity was found in the cells of all papillary carcinomas. In the multinodular goiter group, 20 of 25 cases showed no staining while the remaining 5 were focally reactive with CK19. Three of the five were thought to be false positive owing to hemorrhage. Weak and focal CK19 staining was seen in some follicular adenomas. Our observations suggest that the staining features of CK19 may be helpful in differential diagnosis between papillary carcinoma and multinodular goiter showing papillary areas. Focal and pale staining for CK 19 may be seen in multinodular goiter with papillary formations, and this feature should be considered in evaluation.     

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.     

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).     

Diagnostic value of differential expression of CK19, galectin-3, HBME-1, ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: An immunohistochemical tissue microarray analysis

Background Several immunohistochemical markers have been used to aid in the diagnosis of follicular-derived lesions of the thyroid (FDLT). In this study we analyze the diagnostic efficacy of an immunopanel of antibodies to cytokeratin-19 (CK19), galectin-3 (GAL-3), HBME-1, anti-MAP kinase (ERK), ret-oncoprotein (RET), and p16 using a tissue microarray consisting of both benign and malignant FDLT. Design The study cohort consisted of 90 cases of FDLT (53 benign, 37 malignant) embedded in a microarray and immunostained with antibodies to CK19, Gal-3, HMBE-1, ERK, RET, and p16. Staining was scored as positive when >25% of the lesional cells showed positive immunostaining. Results HMBE-1 was expressed in 70% of malignant and 10% of benign FDLT (p value: <0.0001). (CK19 and GAL-3 were positive in 70% and 73% of malignant lesions, respectively, and 34% of benign FDLT (p value 0.0005 and 0.0015, respectively). ERK was positive in 4% of the benign and 32% of the malignant cases (p value 0.0002). p16 was expressed in 2% and 46% of the benign and malignant lesions, respectively (p value 0.0001). RET positivity was identified in 15% of the benign lesions and 27% of the malignant cases (p value 0.0016). Conclusions HBME-1, ERK, and p16 were more specific for malignancy, whereas CK19 and GAL-3 stained benign lesions with a higher frequency and were not specific for malignant FDLT. RET-oncoprotein showed poor sensitivity and specificity.     

Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma

AIMS: The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures. METHODS AND RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.     

甲状腺乳头状癌RET、CK19、TG、Ki-67的表达

目的 研究甲状腺乳头状癌RET、CK19、TG、Ki-67蛋白表达特点及其临床意义。方法 应用免疫组织化学SP法检测RET、CK19、TG、Ki-67蛋白在30例甲状腺乳头状癌、10例结节性甲状腺肿和18例癌旁正常甲状腺中的表达。结果 RET、CK19在乳头状癌的阳性率（66．7％、83．3％）明显高于结节性甲状腺肿和正常甲状腺阳性率（7．1％、25．0％）,两者差异有显著性（P〈0．01）。乳头状癌组及良性病例组TG表达阳性率差异无显著性（P〉0．05）。96．7％的乳头状癌Ki-67阳性细胞数小于10％。结论 RET及CK19在甲状腺乳头状癌表达增加,具有一定的病理诊断价值。     

Combined immunohistochemistry for thyroid peroxidase, galectin-3, CK19 and HBME-1 in differential diagnosis of thyroid tumors

We evaluated some proposed molecular thyroid tumor markers: thyroid peroxidase (TPO), galectin-3, cytokeratin-19, and HBME-1, individually and in combination, by immunohistochemistry in a total of 242 archival thyroid tissue sections. The expression of each individual marker was most helpful for the diagnosis of papillary carcinoma and its follicular variant. However, none of them was sensitive and specific enough to discriminate between Hürthle adenoma and carcinoma. Galectin-3 and HBME-1 could be used as single discriminators between follicular thyroid adenoma and carcinoma, but HBME-1 is the better choice. As a single test, all analyzed tumor markers had sufficient power to predict differentiated thyroid cancer, with sensitivities ranging from 66.5% to 82.2%. The sensitivity was improved by using combinations of some proposed markers. Only two antigens, HBME-1 and TPO, had distinct predictive values for different diagnostic alternatives i.e. a sequential combination improved diagnostic accuracy between follicular thyroid adenoma and the follicular variant of papillary thyroid carcinoma to 92.6% and consequently, between overall benign and malignant thyroid tumors to 89.1%. HBME-1 is the most accurate ancillary stain in discriminating well-differentiated thyroid carcinomas from benign tumors, although the addition of TPO did improve accuracy and served as a useful confirmatory marker.     

Galectin-3 expression in papillary microcarcinoma of the thyroid

AIMS: Galectin-3 is a beta-galactoside binding protein, recently recognized as a promising molecular marker of thyroid malignancy. As reported in several studies, galectin-3 is highly expressed in papillary thyroid carcinoma, but its expression has not been investigated in papillary microcarcinoma, which is a variant of papillary thyroid carcinoma. METHODS AND RESULTS: Using a monoclonal antibody to galectin-3 and the avidin-biotin-peroxidase complex (ABC) immunohistochemical technique, we analysed galectin-3 expression in 63 cases of papillary microcarcinoma. The results showed immunohistochemical reactivity for galectin-3 in 51 (80.9%) cases. Intensity of staining varied from strong or moderate to weak. Galectin-3 localization was mostly cytoplasmic, but also membranous or nuclear in some cells. Immunohistochemical expression of galectin-3 was not found in 12 (19.1%) cases. Most galectin-3 negative microcarcinomas (10/12) were of the non-classical type, i.e. without papillary architecture. Neither the frequency nor the intensity of a positive reaction was related to tumour size. CONCLUSIONS: Galectin-3 gene is expressed at the protein level in most papillary microcarcinomas, although with slightly lower frequency than that reported for clinically evident papillary thyroid carcinoma. The presence of galectin-3 in clinically silent microcarcinomas may indicate that galectin-3 is not related to growth or aggressiveness of papillary thyroid microcarcinomas but rather plays some other role in thyroid tumour biology.     

Expression of HBME-1 and CD56 in follicular variant of papillary carcinoma in children: An immunohistochemical study and their diagnostic utility

Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer in children; and the follicular variant is the second most common variant after the classic subtype. The histological appearance of follicular variant of papillary thyroid cancer (FVPTC), can be mimicked by benign follicular nodules. Pediatric pathologists encountering such lesions with FVPTC-like appearance may err on diagnosing the benign lesions as malignant. In adult patients, several immunohistochemical markers have emerged recently as a useful adjunct to distinguish differentiated thyroid carcinomas from benign follicular lesions. We undertook an inter-institutional retrospective study to establish the diagnostic utility of immunohistochemical staining for HBME-1, Galectin-3 and CD56 in differentiating FVPTC from its benign mimics, follicular adenoma and adenomatoid nodules, in children. Our specific aim of the project was to define the sensitivity and specificity of the three antibodies in FVPTC. Based on institutional diagnoses, a total of 66 cases were obtained: 32 FVPTC and 34 benign follicular nodules that comprised of 23 follicular adenoma and 11 adenomatoid nodules. Five investigators, who were blinded to the original diagnoses, independently reviewed the slides following pre-determined criteria and semi-quantitatively scoring the immunohistochemical staining. The immunohistochemical staining revealed that a combination of positive HBME-1 and negative CD56 result gave 100% specificity and positive predictive value in distinguishing FVPTC from benign follicular nodules. However, the antibody combination suffered from a lower sensitivity (50%). We used a cutoff of 25% positivity of tumor cells in determining positivity of tumor cells to an antibody. In conclusion, our study found a very high specificity and strong positive predictive value for the combination of HBME-1 and CD56 immunohistochemical stains in distinguishing FVPTC from benign follicular lesions.     

甲状腺乳头状癌诊断与鉴别的可靠标记物

目的寻找更好的标记物，用于甲状腺乳头状癌的诊断与鉴别。方法以甲状腺乳头状癌（PTC）为研究组，以甲状腺滤泡状腺瘤（FA）和良性乳头状病变（BPL）作对照组。经自制组织芯片和免疫组化技术，对Twist、Galectin-3、HBME-1、p14^ARF和TPO进行标记，并与CK19对比实验。结果6种指标阳性表达率依次为：PTC组100．0％、95、6％、80．0％、28．9％、15．6％和78．0％：FA组0．0、11．1％、6．7％、75．6％、88．9％和0．0；BPL组7．0％、7．5％、2．5％、77．5％、100．0％和0．0。PTC组与FA和BPL组比较差异均有显著性（P〈0．05）。6种指标的灵敏度、特异度、准确度分别为100.0％、95．6％、80．0％、71．1％、84．4％、78．0；96．g％、90．1％、95．3％、76．5％、94．1％、100．0％和97．7％、92．3％、90．0％、74．6％、90．8％、91．9％。结论在PTC中6种指标阳性表达率最高的为Twist，其次为Galectin-3，因此临床病理工作中标记Twist和Galectin-3鉴别PTC与FA或BPL有实用意义。Twist的灵敏度和准确度最高，CK19特异度最高。因此该2种指标联合使用对于PTC的鉴别诊断最可靠。     

细胞角蛋白19、galectin-3、HBME-1在甲状腺病变上的表达及鉴别诊断意义

目的 研究细胞角蛋白(CK)19、galectin(Gal)-3、HBME-1在甲状腺不同病变表达的特点及鉴别诊断中的应用价值。方法 应用免疫组织化学EnVision法检测了21例结节性甲状腺肿(结甲)、14例毒性甲状腺肿(甲亢)、15例甲状腺滤泡性腺瘤(腺瘤)、13例滤泡性癌、13例滤泡型乳头状癌及48例经典型乳头状癌中单克隆抗体CK19、Gal-3、HBME-1的表达。结果 甲状腺病变中3种标记表达均位于细胞质;CK19、Gal-3、HBME-1的表达在甲状腺良性病变(结甲、甲亢、腺瘤)大多为弱阳性或阴性,而滤泡性癌阳性明显增加、乳头状癌(滤泡型及经典型)大多为中、强阳性,3种标记在甲状腺不同病变的阳性表达率结甲为52．4％(11／21)、9．5％(2／21)、19．0％(4／21),甲亢为50．0％(7／14)、7．1％(1／14)、7．1％(1／14),腺瘤为60％(9／15)、13．3％(2／15)、13．3％(2／15),滤泡性癌为76．9％(10／13)、61．5％(8／13)、53．8％(7／13),滤泡型乳头状癌为：100％(13／13)、84．6％(11／13)、92．3％(12／13),经典型乳头状癌为100％(48／48)、93．8％(45／48)、95．8％(46／48);在甲状腺良性病变(结甲、甲亢、腺瘤)与恶性病变(滤泡性癌、乳头状癌)间3种标记差异均有显著性(P均=0．000);同时3种标记在滤泡样病变即腺瘤、滤泡性癌和滤泡型乳头状癌间亦有显著差异(CK19：P=0．038,Gal-3：P=0．001,HBME-1：P=0．000)。结甲有9例,甲亢有7例,腺瘤有6例3种标记均不表达,滤泡性癌仅有1例,而乳头状癌(滤泡型及经典型)没有病例3种标记均不表达,同一病例有2种以上阳性表达在结甲、甲亢、腺瘤、滤泡性癌、滤泡型乳头状癌和经典型乳头状癌中分别为14．2％(3／21)、21．4％(3／14)、20．0％(3／15)、69．2％(9／13)、92．3％(12／13)、100．0%(48／48),在甲状腺良性病变与恶性病变间以及滤泡样病变间差异亦有显著性(P=0．000)。结论 CK19、Gal-3、HBME-1的检测尤其是联合检测对甲状腺病变的诊断、鉴别诊断具有较高的实用价值。     

Role of cd56 and e-cadherin expression in the differential diagnosis of papillary thyroid carcinoma and suspected follicular-patterned lesions of the thyroid: the prognostic importance of e-cadherin

Introduction: The pathological diagnosis of papillary thyroid carcinoma (PTC) is generally easy on routine sections stained with hematoxylin and eosin (H&E). However, the differentiation of the follicular variant of PTC (FVPTC) from other suspected follicular-patterned lesions of the thyroid is highly difficult. Among these, the lesions for which FVPTC cannot be excluded are classified as well-differentiated tumors of uncertain malignant potential (WDT-UMP). The most common immunohistochemical (IHC) markers used in the differential diagnosis include HBME-1, galectin-3, and CK19. However, none of these markers provide a 100% differential diagnosis. Objective: The present study compared the diagnostic value of CD56 and E-cadherin for the differentiation of FVPTC from the other benign follicular-patterned lesions, with HBME-1, galectin-3, and CK19. Using these markers, the controversial cases within the WDT-UMP group were reclassified. Additionally, the relationship between the reductions in E-cadherin expression with poor prognostic factors was investigated. Materials and methods: The IHC expressions of CD56, E-cadherin, HBME-1, galectin-3, and CK19 were evaluated in 181 thyroid lesions, including 101 PTCs (45 classical variant PTCs and 56 FVPTCs), 20 WDT-UMPs, 20 follicular adenomas (FAs), 20 hyperplastic nodules (HN), and 20 hyperplastic foci of lymphocytic thyroiditis. The results were statistically compared via SPSS. Results: The expressions of all of the markers were statistically significantly different in PTC and follicular-patterned lesions (P<0.05). It was found that the only marker with both sensitivity and specificity above 90% was CD56 negativity (sensitivity 91.1%, specificity 91.7%). The most sensitive and also the most specific double panel was CD56 negativity and galectin-3 positivity (sensitivity 96%, specificity 85%), and the most sensitive and specific triple panel was CD56 negativity, HBME-1 positivity, and galectin-3 positivity (97% and 70%, respectively).     

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.