McCarthy Ryan P, Wang Mingsheng, Jones Timothy D, Strate Randall W, Cheng Liang
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Clin Cancer Res. 2006 Apr 15;12(8):2414-8. doi: 10.1158/1078-0432.CCR-05-2818.
Patients with papillary thyroid carcinoma often have two or more distinct papillary tumors at thyroidectomy. Whether these multifocal papillary lesions are clonally related or whether they arise independently is unknown as previous studies have shown conflicting results. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate tumors from the same patient can be used to define the genetic relationships among the multiple coexisting tumors.
We examined 64 separate tumors from 22 female patients who underwent thyroidectomy for thyroid carcinoma. All patients had multiple and separate papillary carcinomas (range, two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays for three microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22-p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done on the tumors from all patients.
Twenty of 22 (91%) cases showed allelic loss in one or more of the papillary lesions in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between coexisting papillary tumors were seen in 20 of 23 (87%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions was seen in all informative cases.
Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma often arise from the same clone. Thus, intrathryoid metastasis may play an important role in the spread of papillary thyroid carcinoma, a finding that has important therapeutic, diagnostic, and prognostic implications.
甲状腺乳头状癌患者在甲状腺切除术中常出现两个或更多不同的乳头状肿瘤。这些多灶性乳头状病变是克隆相关的还是独立发生的尚不清楚，因为先前的研究结果相互矛盾。对同一患者不同肿瘤中的微卫星改变和X染色体失活状态进行分子分析，可用于确定多个共存肿瘤之间的遗传关系。
我们检查了22例因甲状腺癌接受甲状腺切除术的女性患者的64个独立肿瘤。所有患者均有多发性且相互独立的乳头状癌（范围为2至6个）。使用激光捕获显微切割技术从福尔马林固定、石蜡包埋的组织切片中制备基因组DNA样本。对位于染色体3p25（D3S1597）、9p21（D9S161）和18p11.22 - p11（D18S53）上的三个假定肿瘤抑制基因的微卫星多态性标记进行杂合性缺失检测。此外，对所有患者的肿瘤进行X染色体失活分析。
22例患者中有20例（91%）在分析的三个多态性标记中的至少一个标记的一个或多个乳头状病变中出现等位基因缺失。23例患者中有20例（87%）在共存的乳头状肿瘤之间观察到一致的等位基因缺失模式。在所有信息充分的病例中，多个共存的乳头状病变中均观察到非随机X染色体失活的一致模式。
我们的数据表明，甲状腺乳头状癌患者的多灶性肿瘤通常起源于同一克隆。因此，甲状腺内转移可能在甲状腺乳头状癌的扩散中起重要作用，这一发现具有重要的治疗、诊断和预后意义。
