MOLECULAR MECHANISMS DISTINGUISH FOLLICULAR ADENOMA/FOLLICULAR CARCINOMA

区分滤泡性腺瘤/滤泡性癌的分子机制

• 批准号: 6275528
• 负责人: MARTHA A ZEIGER
• 金额: $ 2.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6275528
• 关键词: adenoma; biomarker; carcinoma; chromosome aberrations; clinical research; cytology; diagnosis design /evaluation; diagnosis quality /standard; enzyme activity; human subject; loss of heterozygosity; molecular oncology; neoplasm /cancer diagnosis; nucleic acid repetitive sequence; telomerase; thyroid neoplasm

Over 28,000 thyroidectomies are performed in the United States annually for suspected malignancy. However, up to 18,000 of these are benign on permanent histology. This phenomenon is due to the fact that fine needle aspirations (FNA) of the thyroid that are suspicious for malignancy ultimately turn out to represent a benign process in 60% of cases. Because of this phenomenon we chose to examine follicular neoplasms of the thyroid for molecular markers that would distinguish a follicular adenoma from a carcinoma. Up to 40 follicular neoplasms of the thyroid were screened by microsatellite polymorphism analysis that might distinguish the two. Although there was no difference between follicular adenomas and follicular carcinomas, Hijrthle cell neoplasms of the thyroid appeared to have greater loss of heterozygosity on chromosomes 1q and 2p that could distinguish Hijrthle cell adenomas from Hijrthle cell carcinomas. These abnormalities could also be demonstrated on FNA samples with 100% sensitivity and 75% specificity; a potential dramatic improvement over what can now be accomplished by cytology. Because Hiirthle cell neoplasms of the thyroid represent a very small percentage of thyroid carcinomas that still left the clinical dilemma of distinguishing follicular adenomas from carcinomas as well as lesions that were suspicious for papillary thyroid carcinoma. We, therefore, examined follicular neoplasms and lesions that were suspicious for papillary cancer for telomerase activity. We found that 100% of follicular carcinomas and 67% of papillary thyroid cancer have a positive telomerase activity. As a result of this above work, we are prospectively collecting FNA samples from patients who have suspicious lesions on thyroid cytology. The collaborating institutions include the University of Pittsburgh and Mayo Clinic at Jacksonville. To date we have collected 127 samples and are currently examining the use of telomerase as a marker to distinguish benign from malignant. Should we be able to accomplish this and apply it to FNA then theoretically this technique could result in the obviation of up to 18,000 thyroidectomies performed annually in this country.

在美国每年进行超过28，000例甲状腺切除术 疑似恶性肿瘤 然而，其中多达18，000个是良性的， 永久组织学。 这一现象是由于这样一个事实， 甲状腺针吸检查（FNA）可疑 恶性肿瘤最终在60%的患者中表现为良性过程。 例 由于这种现象，我们选择检查卵泡 甲状腺肿瘤的分子标志物， 从癌细胞中分离出来的滤泡性腺瘤 多达40例滤泡性肿瘤 用微卫星多态性分析筛选甲状腺癌患者 可以区分这两者。 虽然没有什么区别 滤泡性腺瘤和滤泡性癌之间，Hijrthle细胞 甲状腺肿瘤的杂合性丢失更大 在染色体1 q和2 p上，可以区分Hijrthle细胞腺瘤 Hijrthle细胞癌 这些异常也可能是 在FNA样本上显示，灵敏度为100%，特异性为75%; 一个潜在的戏剧性的改善，现在可以完成的， 细胞学 因为甲状腺的希尔氏细胞肿瘤代表了一个非常小的 仍处于临床困境的甲状腺癌的百分比 区分滤泡性腺瘤与癌以及病变 怀疑是甲状腺乳头状癌 因此，我们 检查了可疑的滤泡肿瘤和病变， 乳头状癌的端粒酶活性 我们发现100%的 滤泡癌和67%的乳头状甲状腺癌 端粒酶活性阳性。 由于上述工作，我们 前瞻性地从可疑的患者中收集FNA样本， 甲状腺细胞学上的病变。 合作机构包括 匹兹堡大学和杰克逊维尔的马约诊所。 迄今 我们已收集了127个样本，现正研究 端粒酶作为良恶性鉴别标志物。 我们应该 能够做到这一点，并将其应用于FNA，那么理论上， 这项技术可以避免多达18，000例甲状腺切除术 每年在这个国家举行。