侦测甲状腺癌的新方法


  Oct 17, 2006 (凤凰城) —在上周的美国甲状腺疾病协会第77届年会中,诊断甲状腺癌的新方法和侦测有无扩散到淋巴结的新方法被提出。
  
  【分子指纹提供更早期的侦测】
  新的诊断技巧包括用质谱仪监定甲状腺癌特有的蛋白质模式,可清楚地与健康者的蛋白质模式分辨 ;这是新的监定血清胜肽方法,藉由补体蛋白分解和凝集蛋白得到结果,来自纽约市Sloan-Kettering癌症纪念中心的研究者Andrew Martorella医师和同事指出,这可以作为新的甲状腺癌生物标记。
  
  该研究团队使用质谱仪分析60位转移甲状腺癌病患和200位健康志愿者的血清样本,此技术可正确分类血清样本,敏感度和专一度达95%。
  
  Martorella医师藉由美国甲状腺协会发布新闻指出,本研究结果是显著的,血清胜肽资料有潜力作为分子指纹,可以用来辨识转移甲状腺癌病患和健康者,让医师们得以更早诊断出甲状腺癌。
  
  【使用超音波之诊断再现性更佳】
  复发之甲状腺癌最常发生在颈部淋巴结,最常使用在复发检测的两个方法是全身放射碘造影和血清甲状腺球蛋白,但是会中的一篇新的研究指出,超音波检测胜过这两种方法。
  
  辛辛那提大学的David Steward医师在会中表示,超音波是检测方法中最有敏感度的,他领导一项回溯研究,对许多医疗机构或诊所的的96位甲状腺癌病患比较这3种方式。
  
  这些病患中,22位(22%)经病理确定在初始治疗后有复发/持续疾病达平均7 年(范围从1 – 22年) ,20位的病灶是局部的,2位有远端转移(骨盆和肺)。
  
  办公室基础的超音波正确地监定出91%的复发病患,血清甲状腺球蛋白检测的敏感度只有68%,放射碘造影只有20%;这3种检测的专一度相似(分别是87%, 79%,和85%);Steward医师认为,超音波还有其它优点,便宜、非侵犯性,且对病患来说很方便。
  
  研究者还指出超音波找到的淋巴结位置特征可用来帮助分辨是良性的淋巴结还是甲状腺癌,若位在III, IV, VI 就是恶性的,且淋巴结显出咽部凹陷或成囊状,则有百分之百的恶性肿瘤阳性预测价值。
  
  【血管生长因子指出转移】
  另一篇研究认为,甲状腺癌分布到淋巴结是因为自然产生的蛋白质「血管内皮生长因子D (VEGF-D) 」过度表现,检测此一因子的表现状态也有助于监别乳突性甲状腺癌(PTC)和滤泡性甲状腺癌(FVPC)。
  
  此研究由麻塞诸塞纪念医院Ashraf Khan医师领导的团队所发表,他们使用VEGF-D抗体分析免疫组织化学染色的肿瘤样本,并将阳性标本依照密度分成1+ 到 3+。
  
  Khan医师指出,剩余的甲状腺组织显示阴性或者1+ 染色,相对来说,30件 PTC样本测验仅有3个案例是1+,10 个案例是2+,17例是 3+;这些和FVPC样本有显著差异,FVPC样本有35案例,19件是 1+,10件是2+,6 件是3+。
  
  30件 PTC样本中,19 例检测淋巴结,而这些之中,有8例是淋巴结阳性:这些都显出VEGF-D高度表现,有5例是3+ ,3例是 2+ ;相对来说,35例FVPC样本中,有16例有淋巴结检测,仅有1例是阳性,其染色为 3+。
  
  研究者表示,在PTC比FVPC有更高的淋巴结转移发生率是因为和VEGF-D高度表现有关。
  
  Khan医师认为,虽然VEGF基因家族已有许多被发现且运用于癌症治疗和心血管药物,但是这些资料开启了颈部转移关键监定标记的新视野,也降低了甲状腺肿瘤的复发,也提出了各种甲状腺乳突癌的生物差异性。
  
  美国甲状腺疾病协会第 77届年会:摘要204, SCA2850, 207。发表于October 12 and 14, 2006。

New Approaches to Detecting Th

By Zosia Chustecka
Medscape Medical News

Oct 17, 2006 (Phoenix) — A new method for diagnosing thyroid cancer and new approaches to detecting whether the cancer has spread to the lymph nodes were reported here last week at the 77th annual meeting of the American Thyroid Association meeting.

Molecular Fingerprint Offers Earlier Detection

The new diagnostic technique involves mass spectroscopy to identify a pattern of proteins specific for thyroid cancer, which is clearly different from the pattern of proteins seen in healthy volunteers. This newly identified serum peptide profile, resulting from proteolysis of complement and coagulation proteins, may serve as a novel thyroid cancer biomarker, say the researchers, Andrew Martorella, MD, and colleagues, from the Memorial Sloan-Kettering Cancer Center in New York City.

The team used mass spectroscopy to analyze serum samples from 60 patients with metastatic thyroid cancer and 200 healthy volunteers. The technique correctly classified serum samples from cancer patients with 95% sensitivity and specificity.

"The results of the study are remarkable," Dr. Martorella commented in a press release issued by the American Thyroid Association. "This serum peptide profile has the potential to serve as a molecular fingerprint that distinguishes metastatic thyroid cancer from normal healthy patients, allowing physicians the ability to diagnose thyroid cancer earlier."

Ultrasound Best for Diagnosing Recurrences

When thyroid cancer returns, it most often recurs in the lymph nodes in the neck. The 2 methods used most commonly to test for recurrences are whole-body radioiodine imaging and serum thyroglobulin, but in a new study presented at the meeting, both were outperformed by office-based ultrasound.

Ultrasound came out as the most sensitive method of detection, David Steward, MD, from the University of Cincinnati, in Ohio, told the meeting. He headed a retrospective study comparing the 3 modalities in 96 patients who were attending a multidisciplinary thyroid cancer surveillance clinic.

Of the patients, 22 (22%) had pathologically confirmed recurrent/persistent disease detected at a mean of 7 years (range, 1 – 22 years) after initial therapy. In 20 patients the disease was local, while in 2 patients it was distant (pelvis and lung).

Office-based ultrasound correctly identified recurrent disease in 91% of patients whose cancer had recurred, compared with a sensitivity of 68% with serum thyroglobulin testing and only 20% with radioiodine imaging. All 3 tests had a similar specificity (87%, 79%, and 85%, respectively. But ultrasound also has other advantages — it is "cheaper, noninvasive, and more convenient for patients," Dr Stewart commented.

The researchers also noted that lymph node location, but not size, and specific features on the ultrasound scans could be used to help discriminate benign lymph nodes from ones with thyroid cancer. Location in levels III, IV, and VI were indicative of malignancies, and lymph nodes demonstrating jugular indentation or cystic components had a 100% positive predictive value for malignancy, they commented.

Vascular Growth Factor Points to Metastases

Another pointer suggesting that the thyroid cancer may have spread to lymph nodes comes from an increased expression of the naturally occurring protein vascular endothelial growth factor D (VEGF-D). Testing for expression of this factor may also help to differentiate between papillary thyroid carcinoma (PTC) and follicular variants of papillary carcinoma (FVPC), the meeting heard.

This research was presented by Ashraf Khan, MD, heading a team from the University of Massachusetts Memorial Center in Worcester. They analyzed tumor samples with immunohistochemistry staining using a VEGF-D antibody and graded positive stains from 1+ to 3+ depending on intensity.

Residual thyroid tissue showed negative or 1+ staining, Dr Khan noted. In contrast, of the 30 PTC samples tested, only 3 cases were 1+, while 10 cases stained 2+ and 17 were 3+. There was a significant difference in the intensity of staining between these and the FVPC samples: of 35 cases, 19 stained 1+, 10 were 2+, and 6 were 3+.

Among the 30 PTC cases, 19 were examined for lymph nodes, and of these, 8 were node positive: all of these showed a high expression of VEGF-D, with 5 cases staining 3+ and 3 cases staining 2+. In contrast, among the 35 FVPC cases, 16 had lymph nodes examined, and only one 1 case had positive nodes, and this stained at 3+.

The higher incidence of lymph node metastases seen in PTC compared with FVPC appears to be related to the expression of VEGF-D, the researchers said.

Dr. Khan commented that the VEGF gene family has already found many uses in cancer treatment and in cardiovascular medicine, "But these data open a new window in identifying key markers in cervical metastasis and reducing the recurrence of thyroid tumors, in addition to suggesting biological differences in the variants of papillary carcinoma."


American Thyroid Association 77th annual meeting: Abstracts 204, SCA2850, and 207. Presented October 12 and 14, 2006.

    
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