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。     

甲状腺乳头状癌中CK19、CD56和VEGF-C的表达及意义

目的 探讨CK19、CD56和VEGF-C在甲状腺乳头状癌(thyroid papillary carcinoma,TPC)中的表达及意义.方法 采用免疫组化EnVision两步法检测51例TPC及49例部分伴乳头状增生的甲状腺良性病变(28例结节性甲状腺肿、21例甲状腺腺瘤)中CK19、CD56和VEGF-C表达.结果 CK19、CD56和VEGF-C在TPC中阳性率分别为100%(51/51)、5.9%(3/51)和70.6%(36/51),而在甲状腺良性病变中阳性率分别为8.2%(4/49)、100%(49/49)和20.4%(10/49).CK19、CD56和VEGF-C在TPC与良性病变之间表达差异均有显著性(P<0.01);VEGF-C在有淋巴结转移的TPC中阳性率为95.2%,高于无淋巴结转移者(53.3%),两者比较差异有显著性(P<0.01).结论 CK19、CD56和VEGF-C联合使用可作为鉴别TPC与甲状腺良性病变的重要参考标记物,VEGF-C对TPC的预后判断具有重要意义.     

联合检测CK19、MC、TPO及CD56在甲状腺乳头状癌病理诊断中的意义

目的探讨甲状腺乳头状癌中CK19、MC、TPO、CD56表达及在临床诊断中的意义。方法采用免疫组化Power Vision法检测669例甲状腺乳头状癌组织及423例甲状腺良性病变(增生结节132例、乳头状增生117例及甲状腺腺瘤174例)中CK19、MC、TPO、CD56的表达,并对其进行分析。结果 669例甲状腺乳头状癌中CK19、MC、TPO、CD56阳性率分别为100%、98.95%、18.98%和43.20%,CK19、MC主要呈弥漫强阳性,TPO、CD56多呈阴性;甲状腺良性病变中CK19、MC、TPO、CD56的阳性率分别为67.14%、13.24%、100%、100%。CK19、MC以阴性或中弱阳性为主,TPO、CD56均为强阳性。CK19、MC、TPO、CD56诊断甲状腺乳头状癌的敏感性分别为100%、98.95%、81.02%、56.80%,特异性分别为32.86%、86.52%、100%、100%。结论 CK19、MC均呈阳性,CD56、TPO阴性对甲状腺乳头状癌的诊断有重要价值,联合应用可提高甲状腺乳头状癌诊断的准确性和特异性。     

Galectin-3、CK19和TPO表达在甲状腺良恶性肿瘤病理诊断中的价值

目的比较甲状腺病变中galectin-3、CK19和甲状腺过氧化物酶（thyroid peroxidase,TPO）蛋白表达的差异,寻找有助于诊断良恶性肿瘤的标志物。方法采用免疫组化EnVision二步法检测134例甲状腺癌（123例乳头状癌、11例滤泡癌）、34例甲状腺腺瘤、20例结节性甲状腺肿和10例桥本甲状腺炎中galectin-3、CK19和TPO蛋白的表达。结果Galectin-3、CK19和TPO在甲状腺乳头状癌（包括主要的3个亚型）与良性病变中的表达差异有显著性（P〈0．01）,在乳头状癌各亚型间和各良性病变之间的表达差异均无显著性（P〉0．05）。滤泡癌和良性病变中galectin-3表达差异有显著性（P〈0．01）。滤泡癌和腺瘤中CK19、TPO的表达差异有显著性（P〈0．05,P〈0．01）。结论甲状腺恶性肿瘤特别是乳头状癌中galectin-3和CK19的表达有增高,而TPO表达缺失。3种蛋白分别是诊断甲状腺肿瘤特别是乳头状癌的有用标志物,联合使用结果更可靠。     

GADD153在甲状腺滤泡样肿瘤中的表达及与CK19、Galectin-3和HBME-1的对比研究

目的 探讨GADD153在甲状腺滤泡样肿瘤中的表达及其鉴别诊断价值,并与CK19、Galectin-3(简称Gal-3)和HBME-1进行对比.方法 应用免疫组织化学EnVision法检测了34例甲状腺滤泡性腺瘤、46例甲状腺滤泡性癌及29例甲状腺滤泡型乳头状癌中GADD153、CK19、Gal-3和HBME-1的表达情况.结果 (1)GADD153的表达位于细胞核,在甲状腺滤泡性癌中的表达大多为中度阳性或强阳性,在滤泡性腺瘤和滤泡型乳头状癌中的表达多为阴性或弱阳性,阳性表达率分别为82.6％( 38/46)、32.4％( 11/34)、10.3％ (3/29),滤泡性癌明显高于滤泡性腺瘤和滤泡型乳头状癌,差异均有统计学意义(x2值分别为20.80和37.48;均P＜0.01).(2)CK19、Gal-3和HBME-1 三种标志物均表达于细胞质,其阳性表达率在滤泡性癌为54.3％( 25/46)、67.4％ (31/46)、58.7％( 27/46),在滤泡性腺瘤为50.0％( 17/34)、29.4％( 10/34)、32.4％( 11/34),在滤泡型乳头状癌为100％( 29/29)、93.1％ (27/29)、89.7％ (26/29),滤泡型乳头状癌与滤泡性腺瘤、滤泡性癌间比较,差异亦均有统计学意义(x2值分别为21.20和8.22;均P＜0.01).(3)根据CK19、Gal-3、HBME-1和GADD153四种标志物表达的强弱分为低表达组(记为0和1+)和高表达组(记为2+和3+),分别计算其在各组的敏感性和特异性.滤泡性腺瘤组敏感性分别为26.5％、8.8％、2.9％和11.8％,特异性为50.7％、52.0％、54.7％和58.7％;滤泡性癌组敏感性分别为19.6％、26.1％、23.9％和65.2％,特异性为41.3％、57.1％、62.0％和92.1％;滤泡型乳头状癌组敏感性分别为96.6％、82.8％、79.3％和3.4％,特异性为77.5％、81.3％、85.0％和57.5％.结论 GADD153对甲状腺滤泡性癌诊断的敏感性和特异性均较好,而CK19、Gal-3和HBME-1则能更好地提示甲状腺滤泡型乳头状癌.四者联合应用能更好地鉴别甲状腺滤泡性肿瘤.     

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。     

CK19、COX-2、hTERT在桥本甲状腺炎合并甲状腺乳头状癌中的表达及意义

目的探讨桥本甲状腺炎(Hashimoto's thyroiditis,HT)与甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的关系及HT癌变的可能机制。方法对HT和HT合并PTC,以及单纯PTC各30例,分别进行HE染色形态学观察,及CK19、COX-2、hTERT免疫组化染色。结果 HT病变区域与癌巢之间可见滤泡上皮细胞过度增生→非典型增生→乳头状癌的移行过渡现象。CK19、COX-2、hTERT在正常甲状腺组织中均未见表达,在HT、HT合并PTC及PTC中呈不同程度的阳性表达,与正常组相比差异有统计学意义(P0.05),同时在HT合并PTC组中,在相对正常的滤泡上皮细胞中阴性,非典型增生的滤泡上皮及乳头状癌组织中阳性表达(P0.05)。结论 HT和PTC关系密切,HT具有一定的恶变潜能。HT伴非典型增生性改变,可能是PTC的早期事件。COX-2和hTERT在HT合并PTC的发生、发展中起着重要作用。CK19可作为早期检测HT合并PTC的参考指标。     

甲状腺乳头状癌中PPM1D的表达和意义

目的探讨甲状腺乳头状癌(papillary carcinoma of thyroid,PTC)中PPM1D蛋白的表达情况及其与临床病理特征和p53的关系。方法应用免疫组化EnVision法检测55例PTC及癌旁正常组织中PPM1D蛋白的表达情况并进行统计处理,分析其与临床病理特征的关系及和p53蛋白表达的相关性。结果 55例PTC中PPM1D的表达(74.5%,41/55)高于癌旁正常组织(10.9%,6/55),差异有统计学意义;PPPM1D的表达与患者年龄、性别、肿瘤大小、组织学类型、淋巴结转移、TNM分期无关,而在间质硬化的病例中表达增强(P<0.05);PTC中PPM1D与p53蛋白表达呈负相关(r=-0.339,P<0.05)。结论高表达的PPM1D与PTC相关,与p53之间可能存在相互作用,在PTC发生、发展中具有重要意义。     

甲状腺乳头状癌中MCM7、CDK2、p27蛋白的表达及意义

目的 探讨MCM7、CDK2及p27蛋白与人甲状腺乳头状癌(papillary thyroid carcinoma,PTC)发生、发展的关系.方法 采用免疫组织化学SP法检测40例PTC、30例甲状腺腺瘤、30例结节性甲状腺肿及20例正常甲状腺组织中MCM7、CDK2、p27蛋白的表达.结果 PTC中MCM7、CDK2蛋白的阳性表达率分别为100.00%(40/40)、80.00%(32/40),两者均明显高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P<0.01,P<0.01).PTC中p27蛋白的阳性表达率为22.50%(9/40),明显低于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P<0.01).PTC中MCM7与CDK2蛋白的表达呈正相关(r=0.550,P<0.01),MCM7、CDK2及p27蛋白的表达呈负相关(r=-0.334,P<0.05;r=-0.413,P<0.01).结论 MCM7、CDK2蛋白的高表达及p27蛋白的低表达变化与PTC可能存在关联,三者联合检测或许可以作为临床早期诊断和评价甲状腺肿瘤细胞增殖活性的潜在的参考指标.     

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.     

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.     

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.     

甲状腺乳头状癌CD151和CK19mRNA表达及意义

目的探讨甲状腺乳头状癌中CD151和CK19 mRNA表达及其意义。方法采用RT—PCR方法检测54例甲状腺的良恶性病变组织中CD151和CK19 mRNA的表达,并与临床及病理资料进行分析比较。结果CD151和CK19 mRNA在甲状腺乳头状癌组中的表达与滤泡性腺瘤组、结节性甲状腺肿组以及正常甲状腺组比较均差异具有显著性（P〈0．01）;CK19 mRNA表达与甲状腺癌淋巴结转移有关（P〈0．05）;在甲状腺乳头状癌中,CD151和CK19基因mRNA的表达呈正相关（P〈0．01）。结论CD151和CK19基因共同参与甲状腺癌的发生、发展,并对淋巴结转移的判断有意义。     

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.     

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。     

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.     

Galectin-3 and HBME-1 expression in oncocytic cell tumors of the thyroid

Oncocytic cell tumors (OCTs) of the thyroid include oncocytic cell adenomas (OCAs) and oncocytic cell carcinomas (OCCs). Oncocytic variant of papillary carcinoma (OVPC) has also been described. These tumors may present similar diagnostic problems as their non-oncocytic counterparts, in both conventional histology and fine-needle aspiration biopsies. Several markers were shown able to distinguish benign from malignant thyroid follicular tumors, galectin-3 and HBME-1 being the most promising ones. Controversial data have been reported on their discriminatory potential in the small series of OCTs so far analyzed. We aimed to assess the role of galectin-3 and HBME-1 in a large series of 152 OCTs (including 50 OCAs, 70 OCCs and 32 OVPCs). The expression of PPAR protein was also evaluated. Using a biotin-free detection system, the sensitivity of galectin-3 was 95.1%, while that for HBME-1 was nearly 53%. The combination of galectin-3 and HBME-1 increased the sensitivity up to 99%. However, for both markers, the specificity was 88%, lower than that reported for non-oncocytic follicular tumors. PPAR protein overexpression was absent in all OCAs tested and present in only 10% of OCCs, confirming previous reports on the low prevalence of PAX8-PPAR translocations in OCT and ruling out its role as a potential diagnostic marker of malignancy.     

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.