Application of serum protein fingerprint in diagnosis of papillary thyroid carcinoma

To find new biomarkers and establish serum protein fingerprint models for early diagnosis and preoperative staging of papillary thyroid carcinoma, we employed SELDI-TOF-MS and bioinformatics tools. A total of 116 samples were analyzed in this study. The first 80 samples were analyzed by SELDI-TOF-MS and two biomarker patterns were identified. Pattern 1 distinguishes patients with papillary thyroid carcinoma from healthy individuals. Pattern 2 distinguishes papillary thyroid carcinoma from benign thyroid nodes. The remaining 29 samples were analyzed on the second day and served as an independent test set. The analysis of this independent test set yielded a specificity of 80.0% and a sensitivity of 88.9% for pattern 1 and a specificity of 80.0% and a sensitivity of 80.0% for pattern 2. Two additional biomarker patterns were identified to distinguish different stages of the papillary thyroid carcinoma (pattern 3) with an accuracy of 77.1% and different pathological types of thyroid carcinoma (pattern 4) with an accuracy of 88.1%. Taken together, the SELDI-TOF-MS technique combined with bioinformatics approaches can not only facilitate the discovery of better biomarkers for papillary thyroid carcinoma but also provide a useful tool for molecular diagnosis in the future.     

不同性质甲状腺结节与微血管密度关系的研究

目的:探讨不同性质甲状腺结节与微血管密度关系,提高认识.方法:分别选取甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,病理切片行常规HE染色及免疫组化SP染色.在高倍视野(×400)下选取5个血管着色密集区进行计数并取其平均数,MVD值=(n1 +n2+n3+n4+n5)/5.结果:(1)甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织平均MVD值分别为(65.54±19.21)个/HP、(54.54±11.76)个/HP、(47.85± 10.92)个/HP、(21.82±7.43)个/HP,甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P＜0.05).甲状腺腺瘤、结节性甲状腺肿MVD值显著高于正常甲状腺组织(P＜0.05).(2)伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者(P＜0.05);男性甲状腺乳头状癌患者MVD值显著高于女性患者(P＜0.05);＞40岁及≤40岁甲状腺乳头状癌患者MVD值间无统计学差异(P＞0.05).结论:甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,且伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者.     

ABCG2蛋白在甲状腺乳头状癌中的表达及临床意义

目的 探讨ABCG2蛋白在甲状腺乳头状癌组织中的表达及其临床意义.方法 收集武汉大学人民医院2000-2006年手术切除及活检的甲状腺乳头状癌标本40例和甲状腺腺瘤标本20例.采用免疫组织化学方法检测甲状腺乳头状癌和甲状腺腺瘤组组织内ABCG2蛋白的表达.利用HPIAS-2000图像分析系统测定ABCG2蛋白在甲状腺乳头状癌及甲状腺腺瘤中表达的平均光密度和平均阳性面积率.结果 甲状腺乳头状癌组织中ABCG2蛋白呈高表达;甲状腺腺瘤中ABCG2蛋白呈低表达;图像分析结果显示两组间差异有显著性意义(P＜0.05).结论 ABCG2在甲状腺乳头状癌组织中的高表达可能参与了甲状腺乳头状癌的发生、发展,而且其在癌组织中的高表达可能参与了甲状腺乳头状癌化疗过程中多药耐药形成.     

Carcinoma of the Thyroid Gland—A 15-Year Survey in Private Hospitals in Sacramento

All cases of carcinoma of the thyroid gland diagnosed at two large hospitals in Sacramento during the 15 year period 1951-1965 were studied. Of the 232 cases diagnosed, 179 or 77.2 percent were papillary carcinoma. It was possible to trace 94 percent of all the patients, with a median follow-up of 6.5 years, and no deaths due to papillary carcinoma of the thyroid were found. The extent of operation did not appear to influence the course of papillary carcinoma of the thyroid.     

DcR3在甲状腺乳头状癌中的表达及临床意义

应用RT-PCR、Westem blot、免疫组化分别检测甲状腺乳头状癌组织与癌旁正常甲状腺组织标本中DcR3mRNA及蛋白的表达情况,探讨DcR3在甲状腺乳头状癌组织中的表达及,临床意义。RT-PCR检测显示,甲状腺乳头状癌中DcR3 mRNA的表达明显高于正常甲状腺组织（P〈0．05）：Western blot提示,DcR3蛋白在甲状腺乳头状癌中表达比正常甲状腺组织高（P〈0．05）;免疫组化显示,DcR3蛋白在甲状腺乳头状癌中高表达（P〈0．05）。DcR3mRNA及蛋白质在甲状腺乳头状癌及正常甲状腺组织间的表达差异有统计学意义（P〈0．05）。DcR3基因及蛋白在甲状腺乳头状癌中高表达,提示DcR3可能促进了甲状腺乳头状癌的发生发展。     

HSP70和P53蛋白在甲状腺乳头状癌中的表达及其与临床病理特征的关系

目的：探讨热休克蛋白70（HSP70）和P53蛋白在甲状腺乳头状癌组织中的表达及其与临床病理特征的关系。方法：应用免疫组织化学Envision法检测35例甲状腺乳头状癌组织、15例甲状腺良性病变组织及15例正常甲状腺组织中HSP70和P53蛋白的表达,分析HSP70和P53蛋白的表达与甲状腺乳头状癌临床病理学特征的关系。结果：甲状腺乳头状癌组织中HSP70和P53阳性表达率明显高于甲状腺良性病变组织及正常甲状腺组织（P〈0．01）。HSP70在甲状腺乳头状癌组织中的表达与是否有颈部淋巴结转移、浸润深度以及AJCC分期密切相关（P〈0．01）,而与年龄、性别、肿瘤的大小以及分化程度无关（P〉0．05）。P53在PTC组织中的表达与组织分化程度、是否有淋巴结转移、浸润深度以及AJCC分期密切相关（P〈0．01）,而与年龄、性别、肿瘤的大小无关（P〉0．05）。HSP70和P53蛋白在PTC组织中的表达呈正相关性（r=0．679,P〈0．01）。结论：HSP70和p53蛋白在PTC中均呈高表达,并有协同作用,两者可作为预测PTC的生物学行为和预后的参考指标：     

Expression of obestatin and ghrelin in papillary thyroid carcinoma

Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto’s thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto’s disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies.     

Psammoma bodies in fine needle aspirate of the thyroid in lymphocytic thyroiditis

Psammoma bodies are concentric, laminated microcalcifications that are regarded as nearly specific markers in the thyroid gland for the presence of papillary carcinoma. While psammoma bodies have been seen rarely in some benign thyroid diseases, there appear to be no reports of psammoma body formation in lymphocytic or Hashimoto's thyroiditis. We report a case of Hashimoto's thyroiditis in which psammoma bodies were identified in a fine needle aspiration specimen of the thyroid and in histologic sections of the right thyroid lobectomy; papillary carcinoma was not found in either specimen. We conclude that psammoma bodies may be seen in any benign process, such as nodular goiter or lymphocytic thyroiditis, that produces reactive papillary hyperplasia of thyroid epithelium, as well as in papillary carcinoma. However, the finding of psammoma bodies in a fine needle aspirate without corroborating cytologic evidence of papillary cancer is still an indication for surgical removal of the thyroid nodule since these structures are reliable markers for occult papillary carcinoma of the thyroid, despite the rarity of their formation in benign diseases.     

分子生物学法分析青少年甲状腺肿物临床病理及特点

探讨青少年甲状腺肿物的临床病理学特点,甲状腺癌的复发、转移和结节性甲状腺肿复发的可能相关因素。按WHO病理分型标准和国际抗癌联盟(UICC)TNM分期标准回顾性分析青少年甲状腺肿物124例及其中部分甲状腺癌和结节性甲状腺肿的随访资料。124例甲状腺肿物患者男女比例约为1 3,甲状腺癌39例(31.5%),其中乳头状癌35例,滤泡癌3例,髓样癌1例;甲状腺腺瘤59例(47.6%),结节性甲状腺肿11例(8.9%),结节性甲状腺肿伴腺瘤7例(5.6%),甲状腺炎5例(4%),甲状舌管囊肿3例(2.4%)。本组资料显示,青少年甲状腺癌以乳头状癌为主,其复发、转移与组织学亚型为弥漫硬化型及甲状腺包膜和其外软组织受侵状态相关。虽然常见淋巴结转移、肺转移以及局部侵犯周围软组织,但患者总体预后较好。结节性甲状腺肿的复发与病变弥漫位于双叶有关,而与患者性别、年龄和是否伴有乳头样及腺瘤样增生关系不密切。     

敲低EDAG抑制乳头状甲状腺癌细胞的增殖

为研究EDAG在人乳头状甲状腺癌病人组织中的表达及在乳头状甲状腺癌细胞中的作用,利用免疫组化检测31例乳头状甲状腺癌癌组织及癌旁组织中EDAG蛋白的表达,并进行数据分析.包装EDAG敲低慢病毒颗粒,感染乳头状甲状腺癌细胞系K1,建立EDAG敲低稳定细胞株,检测EDAG敲低对细胞增殖、克隆形成、周期和凋亡的影响. 结果显示,EDAG蛋白在乳头状甲状腺癌癌组织中异常高表达,而在对应癌旁组织极低表达或不表达.建立稳定敲低EDAG的K1细胞株,敲低效果达到约96%,敲低EDAG后细胞增殖变缓,倍增时间由18.49±0.19 h变为19.47±0.11 h,且克隆形成能力下降,G0/G1期比例升高,无血清培养时凋亡增多.本文报道了EDAG在乳头状甲状腺癌病人中高表达,且敲低甲状腺癌细胞系K1中内源EDAG抑制细胞增殖,降低细胞克隆形成能力,G0/G1期增多,凋亡升高,提示EDAG异常高表达可能在甲状腺癌发生发展中具有重要作用.     

Cytopathology of papillary carcinoma of the thyroid by fine needle aspiration

To delineate the cytologic presentation of papillary carcinoma of the thyroid, the fine needle aspiration smears were studied from 87 surgically proven cases. Six diagnostically useful findings were identified: papillary fronds, monolayered sheets, tissue fragments, intranuclear cytoplasmic inclusions, psammoma bodies and multinucleated giant cells. From 1,500 smears on "cold" nodules of the thyroid, 6 known false-negative and 4 false-positive diagnoses for papillary carcinoma were made. The estimated accuracy of the fine needle aspirate diagnosis of papillary carcinoma is 94%.     

Cytologic features of cribriform-morular variant of papillary carcinoma of the thyroid: a case report

BACKGROUND: While the histology of cribriform-morular variant of papillary thyroid carcinoma has been well documented, its appearance on cytologic smears has rarely been described given the rarity of this tumor. CASE: A 28-year-old woman had a neck lump for an unspecified duration for which she sought medical attention. She was previously well, and there was no significant family history of illness. Fine needle aspiration of the thyroid mass disclosed columnar cells with fine to granular chromatin and nucleargrooves associated with papillary fragments and acinar formation. Occasional groups of epithelial cells forming morules, previously unreported on cytology, were present. An excision specimen of the left thyroid nodule revealed morphologic features of cribriform-morular variant of papillary carcinoma of the thyroid. CONCLUSION: A diagnosis of cribriform-morular variant of papillary carcinoma of the thyroid could be established on fine needle aspiration cytology, prompting exclusion of familial adenomatous polyposis and distinguishing it from other, more aggressive variants of thyroid carcinoma, such as columnar cell carcinoma.     

The potential value of the demonstration of thyroglobulin by immunoperoxidase techniques in fine needle aspiration cytology

The peroxidase-antiperoxidase method for the demonstration of thyroglobulin was performed on 30 fine needle aspiration smears. All of the benign thyroid lesions plus the papillary and follicular carcinomas of the thyroid were positive for thyroglobulin. Two cases of metastatic thyroid carcinoma in lymph nodes were also positive. Medullary carcinoma of the thyroid and ten control smears from various other tissues were negative. This proves the sensitivity and the specificity of the method, which may be used in routine cytology and may add to the accuracy of diagnosing metastatic tumors suspected of being of thyroid origin. The intranuclear cytoplasmic vacuoles in papillary carcinoma of the thyroid were negative for thyroglobulin. This unexpected finding is demonstrated, and a possible explanation is offered.     

Lectin histochemistry in rat thyroid tumours

The thyroid tumours and background goiterous and adenomatous lesions induced in rats with diisopropanolnitrosamine (DIPN) plus methylthiouracil (MTU), and regenerative thyroid tissues after wounding were studied by lectin histochemistry. Ten weeks after cessation of the carcinogen treatments, carcinomas invading the surrounding tissues and blood vessels (13/20) and papillary micronodules (11/20) were formed in the thyroid tissues. In general, the carcinoma lesion was solitary, and the papillary micronodules were multiple in a single thyroid gland. Among the lectins tested, Maclura pomifera (MPA) and Solanum tuberosum (STA) showed specific binding with both carcinoma and papillary micronodule lesions, but not with the background goiterous and adenomatous lesions and regenerative thyroid tissues. The former both lesions showed higher labelling indices with BUdR or 3H-thymidine and poorer thyroglobulin accumulation than the latters, thereby indicating their enhanced proliferative capability and depressed potency of cyto-differentiation. The common cytological and histochemical properties of carcinoma lesions and papillary micronodules allow us to regard the latter as pre-invading carcinoma lesions. The lectins MPA and STA may be, therefore, used as the specific markers of malignancy in rat thyroid carcinogenesis.     

A case of extraadrenal pheochromocytoma with papillary thyroid carcinoma.

A 63-year-old housewife with a history of partial thyroidectomy was referred to our hospital because of a neck mass and abdominal tumor. Aspiration biopsy of the neck tumor revealed the recurrence of papillary thyroid carcinoma. Magnetic resonance imaging (MRI) of the abdomen and urinary and plasma catecholamine levels indicated that the tumor beside the abdominal aorta was an extraadrenal pheochromocytoma. Two tumors were excised and histologic studies confirmed the diagnosis. So far two cases of extraadrenal pheochromocytoma with papillary thyroid carcinoma have been reported. The present case indicates that the presence of papillary thyroid carcinoma should be considered in patients with extraadrenal pheochromocytoma.     

抑癌基因PTEN 在甲状腺乳头状癌中的表达及临床意义*

目的:通过免疫组织化学方法检测PTEN基因在正常甲状腺组织、甲状腺良性肿瘤组织、甲状腺乳头状癌癌组织中的表达水平并进行比较,探讨其对甲状腺乳头状癌诊断和治疗的意义。方法:采用SP免疫组化方法,用已知阳性组织做阳性对照,以磷酸盐缓冲液(PBS)代替一抗做阴性对照,分别作HE染色和免疫组织化学染色。结果:PTEN蛋白在三组组织中的表达差异具有显著性(P<0.001);正常甲状腺组织、甲状腺良性肿瘤组织中的阳性率分别为100%和82.5%,均显著高于甲状腺癌组织中的45%(P<0.05),即PTEN在甲状腺癌中表达显著降低;PTEN在甲状腺乳头状癌淋巴结转移组和无淋巴结转移组阳性表达率分别为15%和60%,差异有显著性(x2=10.91,P=0.001);PTEN在甲状腺乳头状癌在包膜侵犯组和无侵犯组的阳性表达率分别为25.93%和60.61%,差异有显著性(x2=7.22,P=0.007);PTEN在甲状腺癌淋巴结转移组和包膜侵犯组的阳性表达强度显著低于无淋巴结转移和包膜侵犯组(P<0.01),有统计学意义。结论:PTEN基因表达的降低在甲状腺癌的发生和转移过程中起重要作用。     

Anaplastic carcinoma of the thyroid with chondroblastoma features mimicking papillary carcinoma: a case report

BACKGROUND: An unusual case of anaplastic carcinoma of the thyroid arising from a metastatic focus of papillary carcinoma. CASE: The tumor affected a 69-year-old woman with a history of total thyroidectomy for papillary thyroid carcinoma 4 years previously. She presented with a rapidly enlarging neck mass that histologically simulated chondroblastoma. A small, embedded focus of residual follicular variant of papillary carcinoma was present. The patient died of disease 3 months later. CONCLUSION: This "chondroblastoma" variant of anaplastic thyroid carcinoma has not been reported to date.     

Intranuclear cytoplasmic inclusions in aspirates of follicular neoplasms of the thyroid. A report of two cases

Two cases are reviewed in which the presence of intranuclear cytoplasmic inclusions in fine needle aspiration biopsy specimens of the thyroid suggested a diagnosis of papillary carcinoma. Subsequent surgical specimens were consistent with diagnoses of microfollicular adenoma and follicular carcinoma. These cases suggest that the presence of intranuclear inclusions in epithelial thyroid cells is not limited to papillary and medullary carcinoma, as some authors have suggested.     

Nuclear grooves. Valuable diagnostic feature in May-Grünwald-Giemsa-stained fine needle aspirates of papillary carcinoma of the thyroid.

Recent reports have indicated the usefulness of nuclear grooves (clefts or notches) as an additional criterion for the diagnosis of papillary thyroid carcinoma in fine needle aspirates; most of these studies were carried out on alcohol-fixed material stained with the Papanicolaou stain or with hematoxylin and eosin, which yield good nuclear details. In the present study air-dried thyroid aspirates stained with the widely used May-Grünwald-Giemsa stain were evaluated. Nuclear grooves were observed in 88% of the May-Grünwald-Giemsa-stained aspirates from papillary thyroid carcinoma, usually in substantial numbers. A few grooved nuclei were seen in a small percentage of the other thyroid aspirates studied. These results show that nuclear grooves can also be used as a possible marker of papillary carcinoma of the thyroid in May-Grünwald-Giemsa-stained aspirates.     

Incidental Finding of Metastatic Papillary Thyroid Carcinoma in a Patient with Primary Hyperparathyroidism

ObjectiveTo report on the management of a patient with the rare concurrence of primary hyperparathyroidism and incidentally found metastatic papillary thyroid carcinoma in an adjacent lymph node.MethodsWe present a case report, including scintigraphic and histologic documentation, and a summary of the related literature.ResultsPrimary hyperparathyroidism with concomitant occurrence of nonmedullary thyroid carcinoma is rare, occurring in less than 4% of patients. We report a case of a 53-year-old woman with no prior history of endocrine disease with primary hyperparathyroidism and an incidental finding of a concurrent thyroid carcinoma. In this patient, technetium 99m scintigraphy revealed a parathyroid adenoma beneath the inferior pole of the left thyroid bed. Parathyroidectomy was performed successfully with no complications. The final pathology examination showed a large parathyroid adenoma with an incidental finding of a small adjacent lymph node containing metastatic papillary thyroid carcinoma. The patient subsequently underwent total thyroidectomy, and the pathology evaluation revealed papillary thyroid carcinoma, follicular variant.ConclusionTo our knowledge, this case of concomitant primary hyperparathyroidism and papillary thyroid cancer is unique in the way in which the diagnosis of metastatic papillary thyroid cancer was made. The presence of parathyroid adenoma should not exclude the diagnosis of thyroid carcinoma; therefore, careful thyroid evaluation should be considered for all patients with primary hyperparathyroidism. (Endocr Pract. 2007;13:380-383)