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。     

Galectin-3在甲状腺癌中的表达及其临床意义

目的：探讨 Galectin-3在甲状腺肿瘤组织中的表达及其临床意义。方法：运用免疫组织化学方法，检测50 例甲状腺癌(其中甲状腺乳头状癌32例，甲状腺滤泡状癌18例)、45例甲状腺腺瘤及20例正常甲状腺组织中 Galectin-3的表达。结果：50例甲状腺癌中，Galectin-3表达阳性者达45例(90． 0%)，其中29例为强阳性；45例甲状腺 腺瘤中，仅2例(4． 4%)Galectin-3阳性者，且均为弱阳性；20例正常甲状腺 Galectin-3均为阴性。Galectin-3表达阳性 率在甲状腺癌中显著高于甲状腺腺瘤及正常甲状腺(P＜0． 01) 。甲状腺乳头状癌与滤泡状癌 Galectin-3表达阳性率无 显著差异(P＞0． 05) 。淋巴结转移者 Galectin-3表达阳性率与无淋巴结转移者相比无显著差异(P＞0． 05) ，但淋巴结转移 者 Galectin-3阳性表达强度显著高于无淋巴结转移者(P＜0． 05) 。结论：Galectin-3可作为鉴别甲状腺良、恶性肿瘤的重 要参考指标，其表达强度的检测有助于甲状腺癌转移的预测。     

NIS蛋白表达对甲状腺癌诊断及131I疗效预测的相关性研究

目的探讨钠碘同向转运体(Na /I-symporter,NIS)蛋白表达在甲状腺癌诊断及术后131Ⅰ治疗效果预测方面的临床应用价值。方法选取我院1998~2006年病理诊断为甲状腺癌的31例患者,采用免疫组化法检测NIS蛋白在细胞中的表达部位、阳性细胞数及表达强度,并以免疫组化评分(immunohistochemical scores,I HS)表示,研究在不同病理类型甲状腺癌原发灶及转移灶中NIS蛋白的表达情况。结果阳性对照Grave病甲状腺组织中NIS蛋白呈强表达,定位于甲状腺滤泡上皮细胞基底部质膜或周边质膜;阴性对照不表达。31例甲状腺癌原发灶细胞胞浆均为NIS阳性表达,其中80.65%的患者IHS≥4分;30例转移灶中,除2例不表达外,其余为胞浆阳性。转移灶与原发灶中NIS蛋白表达具有正相关;甲状腺癌原发灶NIS蛋白表达与甲状腺癌病理类型有关,在乳头状癌(PTC)中最强,滤泡状腺癌(FTC)中次之,滤泡型乳头状癌(fvPTC)中表达较弱。结论NIS蛋白表达在甲状腺癌中主要定位于胞浆,其摄碘障碍可能主要是错误定位的结果。NIS蛋白在不同甲状腺疾病组织中的表达差异有助于甲状腺良、恶性疾病,尤其是FTC与滤泡型腺瘤的鉴别诊断,也有助于不同病理类型甲状腺癌的鉴别。原发灶NIS蛋白表达水平对预测转移灶131I疗效有帮助,NIS蛋白的免疫组化检测有广阔的临床应用前景。     

分化型甲状腺癌的诊断和治疗

分化型甲状腺癌包括乳头状腺癌(病理可细分为单纯乳头状癌、乳头-滤泡混合性癌、乳头状腺癌滤泡样变和有包膜的变异等类型)、滤泡状腺癌(病理可分为微小浸润有包膜的滤泡状腺癌、中度血管浸润性滤泡状腺癌等)。也有作者将许特尔(H櫣rthle)细胞癌列于此分类。乳头状腺癌约占甲状腺癌总数的70%,此型分化好,生长缓慢,恶性程度低,显微镜下肿瘤呈乳头状,由圆形上皮细胞组成;滤泡状腺癌约占15%,此型发展较快,属中度恶性,且有侵犯血管倾向。显微镜下滤泡状腺癌很难与正常甲状腺组织区分,包膜及血管受侵可与滤泡状腺瘤鉴别。尽管近年基因分子生物学…     

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。     

p27及Ki-67对鉴别良、恶性甲状腺滤泡状肿瘤的价值

目的 探讨p17及Ki－67联合检测对于良、恶性甲状腺滤泡状肿瘤的鉴别价值。方法 采用S－P免疫组化法检测53例甲状腺泡状肿瘤（滤泡状腺瘤20例，滤泡状腺癌33例）p27和Ki－67的表达指数（LI）。结果 p27蛋白水平在正常甲状腺组织表达最高，滤泡状腺瘤次这，滤泡状腺癌最低；而Ki－67在正常甲状腺组织几乎不表达（LI＜0．01％），滤泡状腺癌最高，滤泡状腺瘤次之。滤泡状腺瘤与腺癌的p27和Ki－67标记指数相比较差异有显著性意义（P＜0．001），p27在甲状腺滤泡状腺癌、腺癌两类的最佳分界值为LI＝28．3；Ki－67的最佳界值为LI＝10．85。结论 p27和Ki－67的检测可有效的区别良、恶性甲状腺滤泡状肿瘤，也有助于术前甲状腺针吸细胞学对滤泡状腺癌的诊断。     

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。     

二肽氨基肽酶Ⅳ活性在细胞学标本的诊断应用以鉴别甲状腺滤泡型腺瘤和腺癌

二肽氨基肽酶Ⅳ(DPPⅣ)活性测定是在细胞学标本中检测甲状腺滤泡型腺癌的最敏感和特异的标记物,它不依赖于细胞学特点,优于其他临床征象。日本Noguchi甲状腺临床和医院基金会病理科和外科复习1 999～2 0 0 0年收集的滤泡型甲状腺癌细胞学标本,1 9例真阳性、2 6例真阴性、1 6例假阴性和1 8例假阳性的细胞学特征,测定3 5例甲状腺滤泡型癌和44例甲状腺滤泡型瘤的DPPⅣ活性,并分析其肿瘤大小、病人年龄、血清甲状腺球蛋白值及超声图像表现。分析结果示甲状腺滤泡型腺癌和腺瘤的男女比分别为1 .0∶3 .4和1 .0∶4.5 (P =0 .60 ) ,平均年龄分别…     

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。     

MUC1在甲状腺癌及甲状腺良性病变组织中的表达及意义

目的检测多态性上皮粘蛋白 (polymorphicepithelialmucin ,PEM ,又名MUC1)在甲状腺癌及甲状腺良性病变组织 (结节性甲状腺肿 ,甲状腺腺瘤 )中的表达 ,探讨其在甲状腺癌诊断和免疫治疗中的意义。方法采用免疫组化方法检测 6 8例甲状腺癌及 18例甲状腺良性病变组织、10例甲状腺正常组织中MUC1的表达。结果甲状腺癌组织中MUC1阳性表达 5 1例 ,免疫组化染色表现为胞浆内深棕色或棕黄色颗粒 ;结节性甲状腺肿 ,甲状腺腺瘤MUC1阳性表达 4例 ,甲状腺滤泡上皮腺腔缘为黄色或棕黄色颗粒 ;正常甲状腺组织中阳性表达 1例。MUC1在甲状腺癌组织中的阳性表达率与甲状腺良性病变组织及甲状腺正常组织相比 ,差异有显著性 (χ2 =17 2 0 ,P <0 0 1)。MUC1在甲状腺癌组织中阳性表达与甲状腺癌的病理类型和颈淋巴结有无转移无关 (χ2 =0 72 ,P >0 0 5 )。结论MUC1在甲状腺癌组织中的表达及其分布特点可作为甲状腺癌的鉴别诊断指标。     

CD10在甲状腺疾病中的表达及意义

目的研究CD10在甲状腺疾病中的表达及意义。方法收集70例甲状腺良、恶性病变组织，其中15例滤泡性腺瘤、15例腺瘤性甲状腺肿、30例乳头状癌和10例滤泡性癌。采用免疫组织化学的方法检测CD10在上述病变中的表达。结果9例滤泡型乳头状癌中，7例表达CD10，CD10阳性率为77％。10例滤泡性癌中，8例表达CD10，阳性率为80％。而在滤泡性腺瘤和腺瘤性甲状腺肿及21例普通型乳头状癌组织中CD10均不表达。CD10在滤泡型乳头状癌和滤泡性癌中的阳性率显著高于滤泡性腺瘤和腺瘤性甲状腺肿中的阳性率（P〈0．01）。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。     

Encapsulated papillary neoplasms of the thyroid. A study of 14 cases followed for a minimum of 10 years

Fourteen cases of encapsulated papillary thyroid neoplasm in which extracapsular extension was not observed and a minimum of 10 years follow-up was available are herein presented. The cases were divided into three categories: encapsulated papillary carcinomas (five cases), which had cytologic features typical of papillary thyroid carcinoma (vesicular or indented nuclei) and an entirely or predominantly thick capsule with capsular invasion; encapsulated papillary neoplasms of undetermined malignancy (seven cases), in which the cytologic features were also typical of papillary carcinoma but the capsule was predominantly thin (less than 0.1 mm thick) or was thick without capsular invasion; and follicular adenomas with papillae (two cases), which resembled follicular adenomas cytologically (rounded, stippled nuclei and Hürthle cell change) but contained a significant number of papillary structures (both cases had an entirely or predominantly thin capsule). The only evidence of malignant behavior in the entire series was a cervical lymph node metastasis in one case of encapsulated papillary carcinoma; the "encapsulated papillary neoplasms of undetermined malignancy" were so labeled because other authors have reported "encapsulated papillary carcinomas without capsular invasion" and it was therefore thought that the malignant potential of this category is as yet best considered undefined.     

Downregulation of p27KIP1 and Ki67/Mib1 labeling index support the classification of thyroid carcinoma into prognostically relevant categories.

The cyclin-dependent kinase inhibitor p27KIP1 has been proposed as a valuable prognostic indicator for a variety of human neoplasms. Immunohistochemical reactivity for p27KIP1 and the proliferation marker Ki67/Mib1 were investigated in 90 thyroid carcinomas of follicular cell origin. The neoplasms were divided into three prognostic groups on the basis of their morphologic features: group 1, well-differentiated papillary or follicular carcinomas with favorable pathologic features (43 papillary carcinomas and 4 minimally invasive follicular carcinomas); group 2, papillary or follicular carcinomas with unfavorable pathologic features (21 poorly differentiated carcinomas and 2 papillary carcinomas, tall cell variant); and group 3, undifferentiated, or anaplastic, carcinomas. p27KIP1 expression (p = 0.007) and Ki67/Mib1 labeling index (p = 0.02) showed a strong correlation with the subdivision of the thyroid carcinomas in the three prognostic groups with a significant linear trend for tumors with low p27KIP1 (p = 0.002) and high Ki67/Mib1 labeling index (p = 0.005) to segregate into the unfavorable categories (groups 2 and 3). Low p27KIP1 expression, but not cellular proliferation, was related to adverse prognostic factors, such as large tumor size (p = 0.03) and extrathyroidal extension (p = 0.01), but the correlation was not independent of the subdivision in the three groups. Low p27KIP1 expression (p = 0.03) and high proliferative rate (p = 0.02) were associated with poor survival, reflecting the close association between patient morbidity and mortality rates and tumor differentiation. No significant association could be seen between p27KIP1 or cellular proliferation and clinicopathologic parameters (e.g., age, sex, tumor size, extrathyroidal extension, vascular invasion, lymph node metastases, distant metastases, tumor stage, and survival rate) within any of the groups, or the histologic diagnosis of papillary versus follicular carcinoma irrespective of their degree of differentiation. Modulation of p27KIP1 and cellular proliferation patterns in thyroid carcinoma correlate with tumor differentiation and support the morphologic classification of thyroid carcinoma into prognostically relevant categories.     

Clinicopathologic significance of histologic vascular invasion in papillary and follicular thyroid carcinomas

BACKGROUND: The association of angioinvasion with tumor aggressiveness in follicular and papillary thyroid carcinoma remains unclear. This study addresses this problem focusing on clinicopathologic relevance of angioinvasion in the treatment of papillary thyroid carcinoma and follicular thyroid carcinoma. METHODS: From a university hospital database, 358 patients with papillary thyroid carcinoma or follicular thyroid carcinoma were randomly selected. Their charts were retrospectively analyzed and divided into papillary thyroid carcinoma and follicular thyroid carcinoma groups. Each group was subdivided into angioinvasive and nonangioinvasive tumor subgroups. All data were analyzed using Student's t-test, Mann-Whitney rank sum test, chi-square test, and Fisher's exact test. RESULTS: There were 289 women and 69 men, ages 18 to 89 years. Papillary thyroid carcinoma (86%) was more frequent than follicular thyroid carcinoma. Most patients had nonangioinvasive tumor (90.2%). After a mean followup of 43.6 months, there were no significant differences between papillary thyroid carcinoma subgroups for local recurrence (p = 0.69), persistent elevated serum thyroglobulin (p = 0.568), and distant metastasis rates (p = 0.422). No death related to the cancer was observed in both papillary thyroid carcinoma subgroups (p = 1), except for one death resulting from a concomitant nasopharyngeal cancer. The longterm prognosis was less favorable for angioinvasive papillary thyroid carcinoma based on AJCC (American Joint Committee on Cancer staging), AMES (age, distant metastasis, tumor extent, and size), and MACIS (distant metastasis, age, completeness of primary tumor resection, local invasion, and tumor size), but the angioinvasive papillary thyroid carcinoma were larger than nonangioinvasive papillary thyroid carcinomas. The short-term clinical outcomes in both follicular thyroid carcinoma, after a mean followup of 72.3 months, were comparable in terms of local recurrence (p = 0.34), persistent elevated serum thyroglobulin (p = 1), and distant metastasis (p = 0.597). There was no death related to cancer in both follicular thyroid carcinoma subgroups (p = 1). There were no significant differences between both follicular thyroid carcinoma subgroups for longterm prognosis. CONCLUSIONS: Our results indicate that angioinvasion does not adversely influence short-term outcomes or longterm prognosis in follicular thyroid carcinoma and short-term outcomes in papillary thyroid carcinoma. Angioinvasion is a postoperative pathologic finding that does not justify an ominous prognosis or drastic therapeutic measures.     

Analysis of ultrasound B-mode histogram in thyroid tumors

B-mode histograms of preoperative ultrasound texture were correlated to final pathological diagnoses and findings in 50 thyroid tumors (18 follicular adenomas, 6 follicular carcinomas and 26 papillary carcinomas) and 10 cases without any thyroid disease. Histograms were taken in the region of interest (ROI) and in the control area of the normal thyroid tissue. The following parameters, after subtracting the statistics of the control region from that of ROI, were evaluated; the difference of mean (D1), of standard deviation (D2), of skewness (D3), and of krutosis (D4). Likewise, Maharanobis distance (MD) was also studied. D1 was lower in papillary carcinomas than in follicular adenomas, and diminished by the relative proportion of some pathological findings, D2 and D3 of papillary carcinomas was higher than those of follicular adenomas. MD, having a significant correlation to D1 (r = -.8), revealed similar relationship with pathology as that of D1. No significant difference was observed between normal thyroid tissue and follicular adenoma, nor between follicular adenoma and follicular carcinoma in any parameter. MD showed the best correlation to malignancy. The criterion which judges the the tumor with D1 less than -2.5, or D2 more than 1 to be malignant, was expected to have sensitivity of 83% and specificity of 88%.     

Clinical Relevance of Vascular Endothelial Growth Factor for Thyroid Neoplasms

Angiogenesis is of vital importance during the development and progression of solid tumors. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and could be produced by some cancer cells. To investigate the clinical relevance of VEGF in the tumorigenesis of human thyroid, an immunohistochemical study was performed on archival materials of follicular adenomas (n= 13), Hürthle cell adenomas (n= 6), papillary carcinomas (n= 76), follicular carcinomas (n= 12), Hürthle cell carcinomas (n= 2), and anaplastic carcinomas (n= 8). Patterns of VEGF expression were analyzed in relation to histologic subtypes of thyroid tumors and were correlated to biologic indicators of papillary carcinoma. All papillary carcinomas and Hürthle cell neoplasms revealed a strong, diffuse staining reaction, whereas anaplastic carcinoma usually exhibited weak and infrequent immunoreactivity. VEGF levels were usually higher in follicular adenomas than in follicular carcinomas. With regard to prognostic value, VEGF expression did not correlate with tumor size, extent of invasion, or scores on the AGES system (i.e., patient age, tumor size, histologic grade, tumor extent, distant metastasis) or the MACIS system (i.e., metastasis, age, completeness of resection, invasion, tumor size) for papillary carcinomas (p > 0.05, respectively). The results of the current study indicate that VEGF may play a role in the development of human thyroid cancer. Determination of the angiogenic phenotype may have limited prognostic value for patients with papillary carcinoma.     

A population-based analysis of survival factors in differentiated and medullary thyroid carcinoma.

OBJECTIVE: The study purpose was to determine survival and prognostic factors for differentiated thyroid carcinoma (DTC). METHODS: Cases of DTC were extracted from the Surveillance, Epidemiology and End Results database from 1988 through 1998. Kaplan-Meier survival analysis was conducted for papillary, follicular, and medullary histologies. Cox proportional hazard analysis was used to examine the influence of age, gender, tumor size, local extension, and cervical node involvement on overall survival. RESULTS: A total of 18,118 cases were identified, including 15,820 (87.3%) papillary carcinomas, 1799 (9.9%) follicular carcinomas, and 499 (2.8%) medullary carcinomas. Mean survival (10-year survival) was 122 (87.7%), 117 (80.2%), and 108 (73.7%) months for papillary, follicular, and medullary tumors, respectively. For each histology, increasing age, male gender, and degree of local extension substantially reduced survival. Cervical metastasis did not influence survival for papillary or follicular carcinomas but approached significance for medullary carcinoma (P = 0.065). CONCLUSIONS: Degree of local extension in thyroid carcinoma should be subclassified to more accurately determine prognosis. Treatment of the neck should be considered for medullary thyroid carcinoma.     

Prognostic factors of insular versus papillary/follicular thyroid carcinoma

The study aims were to characterize patients with insular thyroid cancer and to provide data on patient outcome after surgical therapy. We compared nine patients with insular thyroid cancer at the Department of Surgical Science of "La Sapienza" University of Rome with 27 patients of similar age and tumor size who had follicular and papillary cancer, for a minimum follow-up period of 24 months (range, 24-72 months). All of the patients examined underwent total thyroidectomy. Vascular invasion was observed in 44.4 per cent of insular carcinomas (P < 0.05 vs papillary carcinomas). No significant differences were observed regarding diagnostic method, multifocality, tumor nodes metastases (TNM), or stage. The death rate of patients with insular carcinoma (33.3%) was found to be higher than that of patients with follicular carcinoma (P < 0.05) and papillary carcinoma (P < 0.01). Relapsing lymph-node pathologies were observed in 4 patients (44.4%) with insular carcinoma (P < 0.05 vs those with follicular and papillary carcinomas). Distant metastases were observed in 66.6 per cent of insular carcinomas (P < 0.005 vs follicular carcinoma and P < 0.001 vs papillary carcinoma). At the end of follow-up, 2 patients (22.2%) with insular carcinoma were disease-free (P < 0.001 vs those with follicular and papillary carcinomas). Our study demonstrates an unfavorable prognostic role of the insular phenotype of thyroid cancer, such that this tumor can be classified as an autonomous clinical and pathological entity.