甲状腺乳头状癌患者外周血人斯钙素-1水平及其临床意义

目的 探讨人斯钙素（hSTC-1）在甲状腺乳头状癌患者外周血中的表达水平及其临床意义。方法 采用逆转录-聚合酶链反应（RT-PCR）检测53例甲状腺乳头状癌患者和20例甲状腺良性肿瘤患者外周血中hSTC-1的表达水平,并与临床病理特征进行分析。结果 hSTC-1 mRNA在甲状腺乳头状癌患者外周血中的阳性表达率为39.62％（21／53）,在甲状腺良性肿瘤患者外周血中则无阳性表达。甲状腺乳头状癌有淋巴结转移患者的hSTC-1 mRNA阳性表达率为66.67％,显著高于无淋巴结转移者的21.88％（P＜0.05）。hSTC-1 mRNA在甲状腺乳头状癌患者中的表达与性别、年龄、临床分期无关。半定量水平检测显示,hSTC-1 mRNA在甲状腺癌患者外周血中的表达量与淋巴结转移有关,亦与性别、年龄、临床分期无关。结论 应用 RT-PCR检测外周血hSTC-1 mRNA有助于甲状腺乳头状癌患者的诊断和淋巴结转移的判断。     

甲状腺乳头状微小癌的临床生物学特性研究

目的：研究甲状腺乳头状微小癌的临床生物学特性，探讨更加合理的微小癌外科处理原则。方法：选取天津医科大学附属肿瘤医院自2003年1月至2006年12月间收治的具有完整病历记录的甲状腺乳头状癌383例，按国际最新甲状腺肿瘤的组织学分类标准分型，统计分析其中微小癌的发生率、性别比例、好发年龄、颈淋巴结转移程度、区域淋巴结转移规律等临床生物学特性。结果：所有病例中甲状腺乳头状微小癌110例，发生率为28．7％。微小癌可同时合并其他组织学变型，其中硬化型最常见，发生率为20．9％；侵袭转移能力较高的高细胞型占3．6％。微小癌在性别及年龄分布上与总体甲状腺乳头状癌相比无明显差异（P〉0．05）。383例甲状腺乳头状癌颈淋巴结转移率为74．7％，而微小癌颈淋巴结转移率为20．0％，低于总体淋巴结转移率（P〈0．05）。在所有转移性甲状腺乳头状微小癌中．90．9％的病例出现Ⅵ区淋巴结转移，仅2例为跨越Ⅵ区直接转移至其它区域。此外所有病例中远处转移（肺）1例，微小癌未见远处转移。结论：甲状腺乳头状微小癌较乳头状癌总体淋巴结转移率低，但亦可合并有高侵袭性组织学变型，可在早期发生颈淋巴结转移，因此不可全部按照Ⅰ期甲状腺癌处理。90．9％微小癌的淋巴结转移是以Ⅵ区为第一站。此区淋巴结阳性，具有指导术式选择的作用。     

甲状腺肿瘤端粒酶逆转录酶mRNA的表达

目的　探讨端粒酶活性在甲状腺肿瘤中的诊断价值。方法　用核酸原位杂交检测了 2 0例甲状腺乳头状癌 ,2 0例甲状腺滤泡状癌 ,9例甲状腺腺瘤端粒酶逆转录酶 (TERT)亚基的mRNA。结果　 2 0例甲状腺乳头状癌阳性检出率为 90 % ,2 0例甲状腺滤泡状癌阳性检出率为 85 % ,明显高于 9例甲状腺腺瘤的阳性检出率 (11.1% ,P <0 .0 1)。结论　端粒酶活化在甲状腺癌的发生过程中起重要作用 ,端粒酶可以作为一种有效的恶性肿瘤标记物用于甲状腺癌的诊断。     

信息动态

甲状腺癌是最常见的内分泌系统恶性肿瘤,发病率有逐渐增高的趋势[1].甲状腺癌有4种类型,即乳头状癌、滤泡状癌、未分化癌和髓样癌[2].乳头状癌和滤泡状癌又被称为分化型甲状腺癌(differentiated thyroid carcinoma,DTC).目前131I治疗是DTC术后主要的治疗方法之一,通过131I治疗后动态观察甲状腺球蛋白(thyroglobulin,Tg)水平的变化可预测肿瘤的转移与复发.     

甲状腺癌的临床病理分析

目的：探讨甲状腺癌临床病理诊断及鉴别诊断。方法：回顾性统计分析90例甲状腺癌的病理材料。结果：男：女为1：4.3，高发年龄为30岁-49岁，乳头状癌73例（81.1％），居首位，其中乳头状微小癌9例，其次为滤泡癌10例（11.1％），髓样癌2例，未分化癌4例，鳞癌1例。结论：病理诊断在甲状腺癌的诊断中起重要作用。     

甲状腺滤泡状癌误诊误治原因探讨（附42例分析）

提高对甲状腺滤泡状癌临床特性的认识，减少误诊误治。方法 回顾分析近10年来收治的42例甲状腺滤泡状癌病例资料，对其诊断，治疗及辅助检查进行探讨。结果 42例均有病理证实为甲状腺滤泡状癌，其中合并有甲状腺乳头状癌2例。术前诊断为甲状腺癌伴颈淋巴结转移14例，甲状腺癌6例，甲状腺肿物12例，甲状腺瘤5例，甲状腺囊肿2例，甲状腺滤泡状癌局部剜除术后2例，甲状腺癌肺转移1例，19例行甲状腺癌联合根治术，15例行1侧腺叶加峡部切除术，5例行甲状腺近全切除术，2例行甲状腺肿瘤剜除术，1例行全甲状腺切除加同位素治疗。结论 术前诊断甲状腺滤泡状癌比较困难。易误诊为甲状腺瘤或囊肿。为减少误诊误治，应重视术前针吸细胞学检查及术中快速冰冻切片检查。     

128例甲状腺癌死亡病例临床分析

报告自１９５４～１９８５年共外科治疗９３７例甲状腺癌病人，其中死亡１２８例，死亡率为１３．６６％。全部死亡病例中乳头状癌，滤泡癌，髓样癌及间变癌的死亡率分别为１０．２８％，１５．０９％，２５．９３％及７５．０％。分化型癌与低分化型癌死亡率差异显著。颈淋巴结转移，远处转移，腺外及周围组织侵犯皆与死亡率有关。其中７０例（５４．２６％）因侵犯局部重要器官或淋巴结转移致死，５８例（４５．３１％）因远处转移致死。肿瘤局部侵犯及血行转移是主要致死因素。     

存活素和CD44V6在甲状腺癌组织中的表达及意义

目的探讨细胞凋亡抑制因子存活素（survivin）和黏附分子CD44V6在甲状腺癌中的表达及其与甲状腺癌侵袭转移的关系。方法采用S-P免疫组织化学染色法，检测100例甲状腺癌和10例正常甲状腺组织中Survivin、CD44V6表达情况。结果Survivin在正常甲状腺组织中无表达，在70例甲状腺乳头状癌（PTC）及30例甲状腺滤泡癌（FTC）中阳性表达率分别为45．7％（32／70）、53．3％（16／30）；CD44V6在70例甲状腺乳头状癌及30例甲状腺滤泡癌中阳性表达率分别为50．0％（35／70）、66．7％（20／30），显著高于正常甲状腺组织；在甲状腺癌组织中Survivin表达与CD44V6表达具有显著相关性（7=0．386，P〈0．05），且两者表达与甲状腺癌的临床分期及有、无淋巴结转移显著相关。结论Survivin和CD44V6表达与甲状腺癌侵袭转移密切相关，且呈协同效应。     

甲状腺乳头状癌合并桥本氏甲状腺炎的临床病理特征

目的：研究合并桥本氏甲状腺炎对甲状腺乳头状癌的临床与病理特征的影响。方法：对我院848例首次手术治疗并经病理确诊为甲状腺乳头状癌的病例进行回顾性分析,按病理是否诊断桥本氏甲状腺炎分为观察组（合并桥本氏甲状腺炎）与对照组（非合并桥本氏甲状腺炎）,分析比较两组间临床病理特征的差异。结果：观察组女性比例更高（95.6% vs 80.6%,P <0.01）,血清甲状腺自身抗体（Tg - Ab 及 TPO - Ab）升高率、术前甲状腺癌诊断率高于对照组（P <0.05）。两组在术前超声检查漏诊率、术中冰冻确诊率、中央区淋巴结转移率、颈侧区淋巴结转移率、肿瘤病灶多发率、甲状腺被膜侵犯率、术后常见并发症发生率、随访期内复发率等方面无显著性差异（P >0.05）。多因素分析显示合并桥本氏甲状腺炎并非甲状腺乳头状癌中央区淋巴结转移的独立风险预测因素（OR =1.286,P >0.05）。结论：甲状腺乳头状癌并发桥本氏甲状腺炎好发于女性,血清甲状腺自身抗体检查有助于桥本氏甲状腺炎术前诊断。并发桥本氏甲状腺炎并不增加甲状腺乳头状癌的术前及术中诊断难度,对甲状腺乳头状癌的临床病理特点也无明显影响。并发桥本氏甲状腺炎的甲状腺乳头状癌可按常规甲状腺癌诊治规范进行治疗。     

血清Tg 、TGAb 与分化型甲状腺癌关系的临床分析

目的：探讨甲状腺球蛋白（Tg）及甲状腺球蛋白抗体（TGAb）在分化型甲状腺癌术后效果评价及随访中作用。方法：采用放射免疫分析法对192例甲状腺癌、68例甲状腺良性病变及31例正常人血清中的Tg、TGAb检测。结果：甲状腺癌组Tg、TGAb阳性率均高于甲状腺良性病变组及正常对照组（P〈0．05）；对135例甲状腺癌手术前后Tg、TGAb对比，术后Tg、TGAb水平均低于术前（P〈0.05）；甲状腺癌并淋巴结转移组的Tg高于无淋巴结转移组（P〈0．05）。结论：Tg、TGAb可作为评价分化型甲状腺癌手术疗效及术后随访的指标。     

Significance of postoperative serum thyroglobulin levels in patients with papillary and follicular thyroid carcinomas

BACKGROUND AND OBJECTIVES: Although there are many factors that affect postoperative serum levels of thyroglobulin (Tg), such levels have been previously used to detect recurrence of papillary and follicular thyroid carcinomas. This study was conducted to elucidate the significance of postoperative levels of Tg in patients with clinical presentations of papillary thyroid carcinoma, follicular thyroid carcinomas, or both. METHODS: To collect data pertaining to patients with thyroid cancer who were treated in Chang Gung Medical Center in Linkou, Taiwan, records relating to a total of 847 patients with pathologically verified papillary or follicular thyroid cancer, all of whom received total thyroidectomy and thyroid remnant ablation with radioactive iodide ((131)I), were studied. To evaluate the clinical significance of postoperative levels of Tg, the patients were categorized into three groups based on postoperative Tg level. Group A was classified as those demonstrating a 1-month postoperative Tg levels less than 1 ng/ml. Group B patients were classified as those displaying a 1-month postoperative Tg levels greater than or equal to 1 ng/ml, but less than 10 ng/ml. Group C patients were classified as those exhibiting a 1-month postoperative Tg levels great than or equal to 10 ng/ml. RESULTS: Of the patients in group A, none presented with distant metastases at the time of diagnosis or during the follow-up period. In group B, 15 patients (3.5%) died of thyroid cancer. In this group, tumor size was an important factor in cancer-related mortality, diagnostic clinical class, and follow-up status. Of the 491 patients in group C, 49 (10.0%) patients died of thyroid cancer. Among the patients in group C, age, histopathologic type, stage of diagnosis, and follow-up Tg values were important factors. Among groups A, B, and C, there were 161 (95.8%), 253 (76.4%), and 129 (37.1%) patients, respectively, with disease-free status at the end of 1998. CONCLUSIONS: Postoperative serum Tg levels can be used as a prognostic indicator in patients with papillary and follicular thyroid cancer. For patients with Tg levels greater than or equal to 10 ng/ml, Tg levels are a useful marker to predict prognosis.     

Clinical presentations and outcomes of surgical treatment of follicular variant of the papillary thyroid carcinomas

BACKGROUND: The follicular variant of papillary thyroid carcinoma (FVPTC) presents with biological and morphological features similar to papillary thyroid carcinoma. Pre-operative diagnosis of FVPTC and its clinical course is important in identifying appropriate surgical procedures. METHODS: This study enrolled 85 patients, 68 females (mean age 41.4+/-13.7 years) and 17 males (mean age 50.1+/-12.3 years) with papillary thyroid carcinomas diagnosed as FVPTC. From the patient database at Chang Gung Medical Center (CGMC), 170 pure papillary thyroid carcinoma cases and 85 with minimally invasive follicular thyroid carcinomas of gender- and age-matched patients were randomly selected as control groups. All patients were categorized into high- and low-risk groups according to AMES criteria. RESULTS: Of the three groups, 7.1% (follicular), 11.8% (FVPTC) and 34.1% (pure papillary thyroid carcinoma) of patients presented with lymph node or soft tissue invasion (P=0.0001). Additionally, 29.4, 11.8 and 2.4% of patients with follicular carcinoma, FVPTC and pure papillary thyroid carcinoma, respectively, presented with distant metastases at the time of diagnosis. Of the 85 FVPTC cases, 75 underwent pre-operative fine needle aspiration cytology (FNAC) examination at CGMC. Only 11 cases were diagnosed pre-operatively with papillary thyroid carcinomas. Kaplan-Meier survival curves for these three groups demonstrated that follicular thyroid carcinoma had a prognosis worse than both papillary thyroid carcinomas. CONCLUSIONS: Most FVPTC cases were diagnosed as follicular neoplasm via pre-operative FNAC. In this study, FVPTC patients had a high ratio of distant metastases, few lymph node metastases and soft tissue invasion. Aggressive treatment was indicated for the high-risk FVPTC patients.     

Expression of c-erbB-2 protein in papillary thyroid carcinomas.

c-erbB-2 protein expression was investigated immunohistochemically in frozen thyroid tissue specimens from 42 patients using a polyclonal sheep antibody. c-erbB-2 immunoreactivity was detected in 12 out of 17 papillary carcinomas, while no c-erbB-2 protein immunostaining was seen in cases of follicular adenoma (five cases), follicular carcinoma (five cases) or medullary carcinoma (one case), nor in cases of non-neoplastic tissue, including normal thyroid tissue from tumour-bearing glands. RNA was extracted from 51 thyroid tissue samples from 34 of the above patients, and c-erbB-2 mRNA was analysed by slot-blot hybridisation. c-erbB-2 mRNA was detectable in all samples, but papillary carcinomas and lymph node metastases showed significantly higher levels of c-erbB-2 mRNA compared to non-neoplastic tissue. The present demonstration of positive c-erbB-2 immunostaining in papillary thyroid carcinomas is contradictory to previous findings on formalin-fixed, paraffin-embedded material, and emphasises the importance of tissue quality for c-erbB-2 protein detection.     

Prognosis in thyroid carcinoma.

All cases of thyroid cancer reported to the Finnish Cancer Registry in 1958-62 were re-examined histologically; 227 cases of thyroid carcinoma were found. The correlation between survival rates and different histologic and clinical features was studied. The survival rates for papillary carcinoma were significantly higher than those for follicular carcinoma, and the latter significantly higher than those for anaplastic carcinoma. The survival rates for medullary carcinoma were similar to those for papillary carcinoma, but there were only 10 medullary tumors. Within papillary carcinoma, vascular invasion correlated with low survival rates. In follicular carcinoma, the encapsulated type, and in anaplastic carcinoma the diffuse small cell type had higher survival rates than other tumors. The extent of the primary tumor and the presence of distant metastases correlated with survival, but the presence of regional metastases did not. The presence of severe compression symptoms correlated with low survival rates. Young patients and females had higher survival rates than old patients and males. In making a postoperative estimation of prognosis it is best to take the histologic type, the extent of the primary tumor, and the presence of distant metastases into consideration. A tentative preoperative prognosis can be bases on the age and sex of the patient and the presence of distant metastases and severe compression symptoms.     

Minimal residual disease in thyroid carcinoma.

The detection of disseminated tumor cells in differentiated (DTC) and medullary thyroid carcinomas (MTC) is one of the main topics in current thyroid cancer research. Immunocytochemistry and polymerase chain reaction (PCR) provide the tools for the identification of a small number of thyroid cancer cells in peripheral blood and cervical lymph nodes. Thyroid-specific markers, such as thyroglobulin (Tg) mRNA and thyroid peroxidase (TPO) mRNA, have been detected with RT-PCR in blood samples of tumor patients and healthy control subjects. To prevent false-positive results, quantitative PCR systems were established. Tumor-specific markers, such as telomerase activity and cytokeratin 20 (CK20), have been detected in various epithelial tumors. Amplification products of these markers were found in blood samples and in fine-needle aspiration (FNA) biopsies of patients with thyroid carcinomas. Using molecular detection of disseminated tumor cells in cervical lymph nodes with CK20 RT-PCR, a higher percentage of involved lymph nodes was detected compared to immunohistochemistry. The results of the presented studies may help researchers to develop more sensitive methods for early tumor cell dissemination, and refine risk groups that might benefit from more extensive surgical procedures or adjuvant therapy. However, the prognostic value of minimal residual disease (MRD) in thyroid carcinoma has to be confirmed in large or multicenter prospective studies.     

Changing Management in Patients with Papillary Thyroid Cancer

Opinion statement The incidence of thyroid cancer has been increasing over the past 30 years, and it is now the seventh most common cancer in women. Papillary thyroid cancer is the most common subtype of thyroid cancer, occurring in 80% of cases. Its main pattern of spread is to cervical lymph nodes, with distant metastases occurring uncommonly. Initial treatment of papillary thyroid cancer involves resection of the primary tumor, with resection of regional lymph nodes if involved with metastatic disease. Postoperative adjuvant therapy consists of radioactive iodine ablation for most patients, followed by thyroid-stimulating hormone (TSH) suppression with thyroxine. An ongoing controversy in the surgical treatment of papillary thyroid cancer is that of extent of thyroid gland and nodal resection. Consensus guidelines recommend total or near-total thyroidectomy, rather than thyroid lobectomy, as the initial procedure of choice, given its advantages of treating potential multicentric disease, facilitating maximal uptake of adjuvant radioactive iodine, and facilitating the post-treatment follow-up by monitoring serum thyroglobulin (Tg) levels. In the hands of an experienced endocrine surgeon, complication rates are comparable to those for lobectomy. Major changes in the management of patients with papillary thyroid cancer over the last 10 years include the use of preoperative neck ultrasound, which can detect nonpalpable cervical lymph node metastases and potentially change the initial operation. In addition, neck ultrasound and measurement of serum Tg levels have taken the place of routine whole body radioactive iodine scans in the postoperative follow-up of patients with papillary thyroid cancer. Recurrent locoregional cervical lymph node disease should be treated by compartmental lymph node dissection, followed by another treatment dose of radioactive iodine. Chemotherapy is generally ineffective for the treatment of metastatic disease. For those patients whose tumor has become radioactive iodine resistant, emerging therapies include redifferentiation agents, antiangiogenic agents, and multi-tyrosine kinase inhibitors.     

Image analysis of papillary thyroid carcinoma fine-needle aspirates: significant association between aneuploidy and death from disease.

BACKGROUND: Papillary thyroid carcinoma is the most common thyroid malignancy in the U.S. As many as half of patients with papillary carcinoma present with cervical lymph node metastases at the time of diagnosis. Metastatic disease involving cervical lymph node tissue has not historically been proven to correlate with a more aggressive course; however, distant metastases worsen prognosis. METHODS: Diagnostic fine-needle aspiration (FNA) smears from 26 primary and metastatic papillary carcinomas underwent Feulgen reaction and were studied by image analysis to determine DNA pattern, proliferation index, and the percentage of cells with DNA content >5C. The medical records of all the patients were reviewed for metastatic disease pattern and survival data. For metastatic pattern, two groups were defined: 1) confined to thyroid/local lymph node metastases/soft tissues of the neck involved by tumor, and 2) distant metastases. RESULTS: Among the 26 patients, 16 had "nonaggressive" DNA patterns described as diploid, abnormal diploid, or tetraploid, and 10 had "aggressive" DNA patterns described as aneuploid. Only 2 of the 16 patients in the "nonaggressive" DNA pattern group developed distant metastases, whereas 5 of the 10 patients in the aneuploid group developed distant metastatic disease. In addition, none of the 16 patients with "nonaggressive" DNA patterns died of disease, whereas 3 of the 10 individuals with DNA histograms interpreted as aneuploid did die of metastatic disease complications. CONCLUSIONS: Aneuploidy identified by image analysis of FNA of papillary thyroid carcinoma is significantly associated with death from papillary carcinoma (log rank test, P=0.027).     

宫颈癌患者外周血中CK19 mRNA和HPV16 mRNA基因的检测及其意义

目的：检测宫颈癌患者外周血标本中的组织特异性标志物(CK19 mRNA)与宫颈癌相对特异性标志物(HPV16 mRNA)的表达。方法：采用RT-PCR技术检测了Ⅰb～Ⅱb期宫颈癌患者的外周血标本30例。远处转移宫颈癌患者8例，妇科良性疾病患者16例，健康人9例：结果：30例外周血标本中3例扩增出CK19的特异性条带，检出率为10．0％(3／30)。远处转移患者CK19检出率为8／8，良性病变患者为0／16，健康者为0／9。30例宫颈癌患者中有10例患者术后宫颈癌标本的免疫组化HPV E6和(或)原位杂交为阳性，均未检测到HPV16 mRNA(0／10)；8例远处转移患者的检出率为12．5％(1／8)，妇科良性病变患者和健康者的检出率分别为0／16和0／9。结论：CK19 mRNA作为宫颈癌患者外周血的检测标志物显示了较好的敏感性和特异性。HPV16 mRNA的检出率较低，临床价值有待进一步研究。