CD10表达在甲状腺滤泡性癌和滤泡型乳头状癌诊断中的作用

目的研究CD10表达在甲状腺滤泡性癌和滤泡型乳头状癌诊断中的作用。方法收集70例甲状腺良、恶性病变组织，其中包括15例滤泡性腺瘤、15例腺瘤性甲状腺肿、30例乳头状癌（包括9例滤泡型乳头状癌）和10例滤泡性癌，采用免疫组织化学方法检测CD10在上述组织中的表达。结果9例滤泡型乳头状癌中，7例表达CD10（77．8％），10例滤泡性癌中8例表达CD10（80．0％）；CD10在非滤泡型乳头状癌、滤泡性腺瘤、腺瘤性甲状腺肿和正常甲状腺组织中均不表达。结论对CD10表达的检测有助于对甲状腺滤泡性癌和滤泡型乳头状癌的诊断。     

Smad4蛋白在结节性甲状腺肿与甲状腺癌并存组织中的表达及其影响

目的:研究结节性甲状腺肿与甲状腺癌并存病变组织中Smad4蛋白的表达及其影响。方法:采用免疫组化SP法对结节性甲状腺肿并存甲状腺癌组织84例、结节性甲状腺肿并存甲状腺瘤50例组织及相应的40例结节性甲状腺肿组织中的Smad4进行检测。结果:Smad4蛋白在甲状腺癌、甲状腺瘤、结节性甲状腺肿组织中的阳性表达率分别为52.38%、74.00%、82.50%,甲状腺癌组织阳性表达率低于甲状腺瘤及结节性甲状腺肿者阳性表达率(P0.05或P0.01)。Smad4蛋白在乳头状癌、滤泡状癌、未分化癌的阳性表达率分别为57.45%、58.33%、23.08%,未分化癌Smad4蛋白阳性表达率低于乳头状癌及滤泡状癌者表达率(P0.05)。结论:检测Smad4蛋白表达对阐述结节性甲状腺肿与甲状腺癌并存病变的生物学行为及评估其预后具有重要意义。     

EGFR与TGF-α在甲状腺乳头状癌中的表达及其临床意义

目的 检测EGFR与TGF-α在甲状腺乳头状癌中的表达和意义。方法 应用免疫组化检测在47例甲状腺乳头状癌、20例良性腺瘤、15例腺瘤旁正常组织中EGFR和TGF-α的表达。结果 EGFR的阳性率分别为乳头状癌59.57%、良性腺瘤25%、瘤旁正常组织6.67%;TGF-α分别为55.32%、20.0%、13.33%;乳头状癌与其他各组比较,均有显著性差异（P〈0.05）;甲状腺乳头状癌中EGFR与TGF-α的同时表达阳性伴淋巴结转移的阳性率为84.21%,而非同时表达阳性或共同阴性表达有淋巴结转移的阳性率为28.57%,两者有显著性差异（P〈0.01）。结论 EGFR和TGF-α表达升高,提示其可能参与甲状腺乳头状癌的发生和发展,以及EGFR和TGF-α的同时表达与淋巴结转移密切相关,提示甲状腺乳头状癌细胞表面可能存在有EGFR和TGF-α的自分泌环。     

EGFR与TGF-α在甲状腺乳头状癌中的表达及其临床意义clinicals

目的检测EGFR与TGF-α在甲状腺乳头状癌中的表达和意义。方法应用免疫组化检测在47例甲状腺乳头状癌、20例良性腺瘤、15例腺瘤旁正常组织中EGFR和TGF-α的表达。结果EGFR的阳性率分别为乳头状癌59.57%、良性腺瘤25%、瘤旁正常组织6.67%;TGF-α分别为55.32%、20.0%、13.33%;乳头状癌与其他各组比较,均有显著性差异(P<0.05);甲状腺乳头状癌中EGFR与TGF-α的同时表达阳性伴淋巴结转移的阳性率为84.21%,而非同时表达阳性或共同阴性表达有淋巴结转移的阳性率为28.57%,两者有显著性差异(P<0.01)。结论EGFR和TGF-α表达升高,提示其可能参与甲状腺乳头状癌的发生和发展,以及EGFR和TGF-α的同时表达与淋巴结转移密切相关,提示甲状腺乳头状癌细胞表面可能存在有EGFR和TGF-α的自分泌环。     

IMP3与CD44v6在甲状腺乳头状癌中的表达及临床意义

目的 探讨IMP3及CD44v6在甲状腺乳头状癌（PTC）中的表达及其临床意义.方法 应用免疫组织化学方法检测30例甲状腺乳头状癌（甲状腺滤泡型乳头状癌10例,非滤泡型乳头状癌20例）,20例甲状腺乳头状癌并颈部淋巴结转移,20例甲状腺良性组织（10例正常组织,10例结节性甲状腺肿）中IMP3和CD44v6表达水平,检测结果用Biosens Digital Imaging System vl.6专业图像分析软件进行定量分析,选择积分光密度（IOD）作为评价参数.结果 IMP3与CD44V6在PTC中的表达高于良性组织中的表达,差异有统计学意义（P ＜0.05）;IMP3与CD44v6在PTC有淋巴结转移中的表达高于无淋巴结转移组织中的表达,差异有统计学意义（P ＜0.05）;IMP3与CD44v6在PTC中的表达呈正相关（r=0.903,P＜0.05）.结论 IMP3与CD44v6在甲状腺乳头状癌中呈高表达,有作为分子标志物协助PTC的诊断及判断PTC的侵袭力及转移力的价值.     

端粒酶活性在甲状腺肿瘤中的表达及意义

目的探讨端粒酶活性在甲状腺癌各病理类型中的表达及其作为甲状腺肿瘤标志物的可能性。 方法采用以PCR技术为基础的TRAP-银染定性和半定量法,检测73例不同种甲状腺组织中的端粒酶活性。 结果正常甲状腺组织中的端粒酶活性阳性率为0（0/8）,结节性甲状腺肿为15.0%（3/20）,甲状腺腺瘤为10.0%（1/10）,乳头状腺癌为75.0%（15/20）,滤泡状腺癌为80.0%（8/10）,髓样癌为100.0%（3/3）,未分化癌为100.0%（2/2）。良恶性组中的端粒酶活性阳性率差异有统计学意义（χ²=36.24,P<0.01）。 结论端粒酶活性在甲状腺癌各个类型中都有高表达,可作为甲状腺肿瘤诊断的理想标志物,尤其是对良恶性甲状腺滤泡性腺瘤的鉴别。端粒酶活性与甲状腺癌组织的分化程度无关,与甲状腺癌的预后可能有关,即端粒酶活性愈强,其预后愈差。     

核干因子在甲状腺乳头状癌中的表达和意义

探讨核干因子(NS)在甲状腺乳头状癌(PTC)中的表达及意义。采用免疫组织化学SP法,分别检测25例甲状腺腺瘤、20例癌旁正常甲状腺组织及58例甲状腺乳头状癌中NS的表达。58例PTC组织中,34例NS蛋白表达为阳性,阳性率58.6%;伴淋巴结转移的30例中,23例表达为阳性,阳性率76.7%;无淋巴结转移的28例表达阳性率46.4%;25例良性甲状腺瘤组织中NS表达阳性率16.0%。NS基因蛋白在PTC中的表达率明显高于良性腺瘤组织和癌旁正常组织。癌旁正常组织和良性腺瘤组织无显著差异性。NS阳性表达率与PTC患者的年龄、性别无关(P0.05),与浸润程度、病理分期、淋巴结转移有关(P0.05)。NS参与了PTC的发生发展过程,高表达的NS基因可能促进PTC的发生发展,并可能是其进展环节中的一个标志性基因。     

粘附分子CD44v6和E—cadherin的表达与甲状腺乳头状癌侵袭转移的关系

目的 探讨粘附分子CD44v6和E－cadherin表达与甲状腺乳头状瘤（PTC）侵袭转移的关系。 方法 应用S－P免疫组织化学方法检测58例甲状腺乳头状癌组织中CD44v6和E－cadherin的表达。结果 甲状腺乳头状癌组织中CD44v6和E－cadherin表达阳性率分别为72．4％和41．4％;CD44v6表达阳性率与PTC的侵袭和转移呈正相关（P＜0．05）,而E-cadherin表达阳性率与PTC的侵袭和转移呈负相关（P＜0．01）,且两种粘附分子在PTC中的阳性表达呈负相关性（P＜0．05）。结论 粘附分子表达与PTC侵袭和转移密切相关,检测CD44v6和E－cadherin的表达可作为判断甲状腺乳头状癌预后的参考指标。     

甲状腺癌中E-cadherin的表达及临床意义

目的 研究E-cadherin在甲状腺癌中的表达及其临床意义。方法 应用免疫组化方法，对19例甲状腺乳头状腺癌，12例甲状腺滤泡伏腺癌和17例甲状腺髓样癌进行了E-cadherin表达的检测。结果 8例（42．1％）甲状腺乳头腺E-cadherin表达阳性，5例（41．7％）甲状腺滤泡状腺癌E-cadherin表达阳性，11例（64．7％）甲关状腺样癌E-cadherin表达阳性。E-cadherin表达在甲状腺癌各病理类型与甲状腺腺瘤之间比较，其阳性率差异有显著性；但在甲癌的三种病理类型之间其阳性率差异无显著性。E-cadherin在甲状腺癌中的表达与年龄有相关性，但与其它各临床病理参数无明显的相关性。结论 在甲状腺上皮细胞表面的E-cadherin具有一定的破坏或功能不正常，但尚不能成为甲状腺癌独立的预后指标。     

核仁素在结节性甲状腺肿与甲状腺乳头状癌中表达及意义的研究

目的:研究核仁素在结节性甲状腺肿及甲状腺乳头状癌中的表达,探讨核仁素在二者疾病发生中的作用及临床意义。方法:采用免疫组化SP法检测36例结节性甲状腺肿及60例甲状腺乳头状癌中核仁素的表达,分析核仁素的表达与性别、年龄、有无转移及病理过程的关系。结果:核仁素在正常甲状腺、结节性甲状腺肿及甲状腺乳头状癌中的总阳性率分别为0、44.4%、100%,差异有统计学意义(P<0.01)。结节性甲状腺肿中核仁素表达于结节期的滤泡上皮细胞核,而胶质贮存期滤泡上皮与结节期的纤维组织不表达。核仁素在伴有转移的乳头状癌组织中表达于细胞核、细胞质与细胞膜,而核仁素在无转移的癌组织中仅表达于细胞核,差异均有统计学意义(P<0.01)。核仁素表达与患者年龄、性别无关(P>0.05)。结论:核仁素参与了结节性甲状腺肿及甲状腺乳头状癌的病理过程,表达随疾病恶化而向核外转移。核仁素可作为判断甲状腺乳头状癌有无转移的客观指标,对指导临床治疗有重要意义。     

组织蛋白酶D在甲状腺乳头状腺癌中的表达及临床意义

目的:研究组织蛋白酶D在甲状腺乳头状腺癌中的表达并探讨其能否成为甲状腺乳头状腺癌独立的预后因素。方法:应用免疫组化方法,对40例甲状腺乳头状腺癌、10例甲状腺滤泡型腺瘤及10例甲状腺正常组织进行了组织蛋白酶D表达的研究,并对可能影响甲状腺癌病人预后的有关因素进行了时序检验单因素生存分析。结果:19例(47.5％)甲状腺乳头状腺癌的组织蛋白酶D表达阳性,而甲状腺滤泡型腺瘤及正常组织的表达均为阴性,差异有显著性(P<0.05)。肿瘤大于4cm及有腺外侵犯者的甲状腺癌组织蛋白酶D阳性表达率(69.23％)明显高于肿瘤小于4cm及无腺外侵犯者(37.04％)(P<0.05)。经时序检验,组织蛋白酶D与甲状腺癌病人的预后并未表现出明显的相关关系。但组织蛋白酶D表达阳性病人的术后复发率为26.3％,表达阴性者复发率为14.3％,有一定的差异。结论:组织蛋白酶D在甲状腺乳头状腺癌中有一定的阳性表达率;当肿瘤大于4cm时,发生转移和侵袭的可能性明显增加,组织蛋白酶D表达阳性者其复发率有升高趋势。     

Fine needle aspiration biopsy of thyroid nodules

The clinical value of the fine needle aspiration of thyroid nodules was evaluated by comparing preoperative cytology to subsequent pathology in 109 patients undergoing thyroidectomy. Preoperative cytology was reported as insufficient cellular material (31 patients), benign goiter (27 patients), follicular neoplasm (22 patients), thyroiditis (12 patients), suspicious for papillary carcinoma (nine patients), Hurthle cell neoplasm (five patients), medullary carcinoma (one patient), lymphoma (one patient), and metastatic adenocarcinoma (one patient). Operative findings demonstrated that the overall sensitivity of fine needle aspiration in diagnosing thyroid neoplasia (carcinoma or adenoma) was 88% and its specificity was 80%. Operation verified the cytologic diagnosis of medullary carcinoma, lymphoma, metastatic adenocarcinoma, and seven of nine papillary carcinomas. Of the five patients with an aspiration biopsy diagnosis of Hurthle cell neoplasm, three patients had carcinoma and one had an adenoma. Four carcinomas and 12 follicular adenomas were found in patients with a cytologic diagnosis of follicular neoplasm. Thyroiditis was confirmed at operation in all 12 patients with this diagnosis on fine needle aspiration. One carcinoma was found in the 27 patients with benign goiter diagnosed on cytology. Fine needle aspiration is a valuable tool that can lead to earlier diagnosis and treatment of thyroid cancer. However, a negative aspiration does not supplant good clinical judgement in determining the need for thyroidectomy.     

Expression of Vascular Endothelial Growth Factor and Presence of Angiovascular Cells in Tissues from Different Thyroid Disorders

Background

Vascular endothelial growth factor (VEGF) is involved in tumor angiogenesis and other pathophysiological processes.

Materials and methods

We studied the localization of VEGF in human thyroid tissues to clarify its involvement in proliferative processes in a variety of thyroid disorders. Immunohistochemical analysis using purified rabbit polyclonal anti-human VEGF or anti-human CD34 antibody and a streptavidin–biotin peroxidase complex detection system was performed on 58 tissue specimens from 53 patients with different thyroid disorders and 5 normal thyroid glands.

Results

Vascular endothelial growth factor was not detected in normal thyroid follicular cells. However, some thyroid tumor cells expressed VEGF in the cytoplasm (papillary carcinoma, 10/18; follicular carcinoma, 1/3; medullary carcinoma, 2/2; follicular adenoma, 3/11; adenomatous goiter, 2/4). In benign follicular adenoma and adenomatous goiter, weak expression of VEGF was found in small areas of the tumor, whereas in malignant thyroid tumors, it was strongly expressed in many cells. However, VEGF was not expressed in anaplastic carcinoma, malignant lymphoma, or Graves’ disease. Angiovascular cells stained with CD34 antibody in tissues from different thyroid disorders reflected statistically significant differences in papillary carcinoma, follicular adenoma, and Graves’ disease compared with normal thyroids, and such cells showed a trend toward increases in medullary carcinoma and adenomatous goiter. In contrast, low vascularity was observed in anaplastic carcinoma, malignant lymphoma, and follicular carcinoma.

Conclusions

Because VEGF probably functions as a hypoxia-inducible angiogenic factor, overexpression of this mediator, concomitant with hypervascularity, may be induced more strongly in malignant thyroid tumors, which need more oxygen to proliferate, than in benign follicular tumors. However, neither VEGF nor CD34 was expressed in anaplastic thyroid carcinoma, which is an extremely poorly differentiated malignant tumor. CD34 but not VEGF was expressed in the hyperplastic thyroid tissues of Graves’ disease composed of nontransformed cells. Thus, the expression of VEGF concomitant with CD34 is suggested to reflect both the transformation and differentiation state of malignant tumors.     

Measurement of cellular DNA content in thyroid tumors by the flow cytometer

Cellular DNA contents measured by flow cytometer were analysed in relation to histopathological classification and clinicopathological findings in 94 patients with thyroid tumors. The DNA determination was carried out on both tumor tissues and surrounding thyroid tissues. As an indicator of tumor growth, proliferative index (PI) and DNA index were calculated from DNA histograms. The PI value (mean +/- SD) was 32.5 in medullary carcinoma, 31.3 +/- 10.2 in follicular carcinoma, 28.2 +/- 6.2 in papillary carcinoma, 21.6 +/- 4.4 in follicular adenoma, and 20.6 +/- 4.4 in adenomatous goiter, respectively, whereas the value in normal thyroid tissues was 4.1 +/- 2.2. PI values in the surrounding thyroid tissues in cases of follicular and papillary carcinomas were significantly (p less than 0.01) lower than those of the corresponding cancer tissues, but they were higher than that of the normal tissues. The DNA index and frequencies of aneuploidy were 1.15 and 50.0% in medullary carcinoma; 1.25 +/- 0.27 and 66.7% in follicular carcinoma; 1.19 +/- 0.25 and 64.2% in papillary carcinoma; 1.01 +/- 0.04 and 9.3% in follicular adenoma; and 1.00 +/- 0.00% in adenomatous goiter. The result implies that PI value and DNA index are relatively correlated with clinicopathological criteria of malignancy of individual thyroid tumors, and they may become a putative tool for determination of the biological malignancy.     

Observer variation of encapsulated follicular lesions of the thyroid gland

Although histologic definition of follicular thyroid lesions is readily available, application of the diagnostic criteria and personal experience may lead to disagreement among pathologists. To investigate interobserver variation in assessment of encapsulated follicular lesions, eight pathologists (four American and four Japanese) reviewed the same hematoxylin and eosin-stained slide of each of 21 cases of thyroid lesions showing encapsulation and follicular growth pattern. In 10% of the cases, there was complete agreement. At least seven pathologists agreed on the diagnosis in 29% of the cases, and at least six in 76% of the cases. American and Japanese pathologists agreed among themselves in 33% and 52% of cases, respectively. The frequency of diagnosis of adenomatous goiter among Japanese pathologists (31%) was considerably higher than that among American pathologists (6%). In contrast, the frequency of diagnosis (25%) of papillary carcinoma among American pathologists was considerably higher than that (4%) among Japanese pathologists. Our analysis revealed three main factors affecting observer variation: 1) interpretation of the significance of microfollicles intimately related to capillaries within the tumor capsule, 2) evaluation of what constituted the type of nuclear clearing indicative of papillary carcinoma, and 3) absence of clear morphologic criteria for separation of adenomatous goiter and follicular adenoma. To reduce observer variation of encapsulated follicular lesions, it will be necessary to provide more explicit criteria for diagnosis.     

Papillary Thyroid Carcinoma Variants

Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but genetic susceptibility and other factors also contribute to the development of papillary thyroid carcinoma. The most common variants include conventional, follicular variant and tall cell variant. However, many other uncommon variants have been described including oncocytic, columnar cell, diffuse sclerosing and solid forms. Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites. Markers such as HBME-1 and CITED1 can assist in separating some difficult cases of follicular variants of papillary thyroid carcinomas from follicular adenomas. Molecular studies have shown that the BRAF V600E mutation is found mainly in papillary and anaplastic thyroid carcinomas. Other molecular markers such as HMGA2 and insulin-like growth factor II mRNA binding protein 3 have been used recently as molecular tests to separate papillary thyroid carcinoma and its variants from follicular adenomas and other benign thyroid nodules.     

Histologic variants of papillary and follicular carcinomas associated with anaplastic spindle and giant cell carcinomas of the thyroid: an analysis of rhabdoid and thyroglobulin inclusions

We describe the histologic variants of papillary and follicular carcinomas associated with 109 spindle and giant cell carcinomas (SGCC) of the thyroid and determine the incidence of rhabdoid and thyroglobulin inclusions in these tumors. In addition, we searched for rhabdoid and thyroglobulin inclusions in 120 papillary carcinomas (PC) (all 15 variants included), 23 differentiated follicular carcinomas (DFC), (6 with insular pattern), 6 poorly differentiated follicular carcinomas (PDFC) and 34 follicular adenomas (FA). The following differentiated thyroid carcinomas coexisted with SGCC: 51 (46.8%) PC, (34 conventional type, 14 tall cell variant and 3 follicular variant), 6 (5.5%) DFC, 1 follicular carcinoma with insular pattern (0.9%), and 3 oncocytic carcinomas (2.8%). Eleven SGCC (10%) and 2 (33%) PDFC showed rhabdoid features, but lacked thyroglobulin inclusions. Thyroglobulin inclusions were found in 10 FA (29%), 8 (17%) follicular variants of PC and in 7 (30.4%) DFC. There were no rhabdoid inclusions in any of these differentiated thyroid tumors. Our findings support the hypothesis that most SGCC result from dedifferentiation or anaplastic transformation although the mechanisms that underlie this transformation remain unknown. The finding that only 1 (0.9%) SGCC was associated with follicular carcinoma with insular pattern contradicts the opinion that this tumor occupies an intermediate position between differentiated and anaplastic carcinomas. Rhabdoid features are markers of PDFC and SGCC while thyroglobulin inclusions are markers of FA and differentiated thyroid carcinomas with follicular phenotype.     

Pathohistologic and immunohistochemical characteristics of thyroid carcinoma

Numerous pathohistologic criteria, difficulties and pitfalls in the process of diagnosing of thyroid carcinoma are discussed. Benign hyperplastic papillae may be present in colloidal cystic goiter and hyperplastic goiter. These structures are lined by cells with normochromatic nuclei and do not disturb the thyroid tissue architecture. Papillae in papillary thyroid carcinoma have cells with ground-glass, hypochromatic nuclei. Follicles inspissated in capsula of follicular or even colloidal adenoma may be evaluated as capsular invasion--diagnostic feature of follicular carcinoma. Undifferentiated thyroid carcinoma is sometimes similar to fibrosarcoma and reveal cellular pleomorphism, anaplasia and numerous foci of necrosis. Medullary thyroid carcinoma with scanty stromal amyloid, its papillary variant and carcinoid-like histologic type consist of oval cells with eosinophilic cytoplasm and dark nuclei.