Segev D L, Saji M, Phillips G S, Westra W H, Takiyama Y, Piantadosi S, Smallridge R C, Nishiyama R H, Udelsman R, Zeiger M A
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
J Clin Endocrinol Metab. 1998 Jun;83(6):2036-42. doi: 10.1210/jcem.83.6.4882.
Follicular and Hürthle cell carcinomas of the thyroid cannot be differentiated from adenomas by either preoperative fine needle aspiration or intraoperative frozen section examination, and yet there exist potentially significant differences in the recommended surgical management. We examined, by PCR-based microsatellite polymorphism analysis, DNA obtained from 83 thyroid neoplasms [22 follicular adenomas, 29 follicular carcinomas, 20 Hürthle cell adenomas (HA), and 12 Hürthle cell carcinomas (HC)] to determine whether a pattern of allelic alteration exists that could help distinguish benign from malignant lesions. Alterations were found in only 7.5% of informative PCR reactions from follicular neoplasms, whereas they were found in 23.3% of reactions from Hürthle cell neoplasms. Although there were no significant differences between follicular adenoma and follicular carcinoma, HC demonstrated a significantly greater percentage of allelic alteration than HA on chromosomal arms 1q (P < 0.001) and 2p (P < 0.05) by Fisher's exact test. The documentation of an alteration on either 1q or 2p was 100% sensitive and 65% specific in the detection of HC (P < 0.0005, by McNemar's test). In conclusion, PCR-based microsatellite polymorphism analysis may be a useful technique in distinguishing HC from HA. Potentially, the application of this technique to aspirated material may allow this distinction preoperatively and thus facilitate more optimal surgical management. Consistent regions of allelic alteration may also indicate the locations of critical genes, such as tumor suppressor genes or oncogenes, that are important in the progression from adenoma to carcinoma. Finally, this study demonstrates that Hürthle cell neoplasms, now considered variants of follicular neoplasms, differ significantly from follicular neoplasms on a molecular level.
甲状腺滤泡癌和许特莱细胞癌，无论是术前细针穿刺活检还是术中冰冻切片检查，均无法与腺瘤相鉴别，然而在推荐的手术治疗方式上却存在潜在的显著差异。我们通过基于聚合酶链反应（PCR）的微卫星多态性分析，检测了83例甲状腺肿瘤（22例滤泡性腺瘤、29例滤泡癌、20例许特莱细胞腺瘤和12例许特莱细胞癌）的DNA，以确定是否存在有助于区分良性与恶性病变的等位基因改变模式。滤泡性肿瘤的信息性PCR反应中仅7.5%出现改变，而许特莱细胞肿瘤的反应中有23.3%出现改变。虽然滤泡性腺瘤和滤泡癌之间无显著差异，但通过Fisher精确检验，许特莱细胞癌在染色体臂1q（P<0.001）和2p（P<0.05）上的等位基因改变百分比显著高于许特莱细胞腺瘤。1q或2p上出现改变在检测许特莱细胞癌时敏感性为100%，特异性为65%（通过McNemar检验，P<0.0005）。总之，基于PCR的微卫星多态性分析可能是区分许特莱细胞癌与许特莱细胞腺瘤的有用技术。该技术应用于穿刺材料可能有助于术前进行这种区分，从而促进更优化的手术治疗。等位基因改变的一致性区域也可能指示关键基因的位置，如肿瘤抑制基因或癌基因，这些基因在腺瘤向癌的进展中起重要作用。最后，本研究表明，目前被视为滤泡性肿瘤变体的许特莱细胞肿瘤，在分子水平上与滤泡性肿瘤有显著差异。
