Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Hum Pathol. 2010 Sep;41(9):1299-309. doi: 10.1016/j.humpath.2010.02.008. Epub 2010 May 14.
Papillary thyroid carcinoma usually presents as a multifocal disease; and tumors often recur in the contralateral thyroid lobe, raising questions concerning their clonal origins. The clonality of tumors appearing simultaneously in both lobes or recurring in the contralateral lobe remains unknown. Accordingly, we examined 25 pairs of bilateral papillary thyroid carcinomas (synchronous or metachronous) and 15 matched metastatic lymph nodes. BRAF gene mutation analysis combined with X-chromosome inactivation was used to evaluate these tumors' clonal origins. Genomic DNA was prepared from paraffin-embedded tissues after microdissection. In total, 62 tumors yielded DNA of adequate quality. Eighteen (18/21, 85.7%) of 21 informative cases showed concordant BRAF status in tumors from both thyroid lobes, being either BRAF mutation positive (12 patients) or BRAF mutation negative (6 patients). Metastatic lymph nodes in 12 patients (12/15, 80%) had a complete concordance of BRAF state with their primaries. Of the 18 studied female patients, 11 were suitable for X-chromosome inactivation assay. Nine cases (9/11, 81.1%) showed the same pattern of inactivation in bilateral tumors. A close correlation was found between BRAF mutation and X-chromosome inactivation analysis. In conclusion, our data provide evidence that bilateral, recurrent, and metastatic papillary thyroid carcinomas often arise from a single clone and that intrathyroidal metastasis may play an important role in the development of bilateral tumors, as well as in the recurrence of this malignancy.
甲状腺乳头状癌通常表现为多灶性疾病；肿瘤常在对侧甲状腺叶复发，这引发了对其克隆起源的疑问。同时出现在两个叶或在对侧叶复发的肿瘤的克隆性仍然未知。因此，我们检查了 25 对双侧甲状腺乳头状癌（同时性或异时性）和 15 个匹配的转移性淋巴结。我们使用 BRAF 基因突变分析结合 X 染色体失活来评估这些肿瘤的克隆起源。从微切割后的石蜡包埋组织中提取基因组 DNA。总共 62 个肿瘤产生了足够质量的 DNA。21 个信息丰富的病例中有 18 个（18/21，85.7%）在双侧甲状腺叶的肿瘤中显示出一致的 BRAF 状态，要么是 BRAF 突变阳性（12 例），要么是 BRAF 突变阴性（6 例）。12 例患者（12/15，80%）的转移性淋巴结与其原发灶的 BRAF 状态完全一致。在 18 例研究的女性患者中，有 11 例适合进行 X 染色体失活分析。双侧肿瘤中有 9 例（9/11，81.1%）出现相同的失活模式。BRAF 突变与 X 染色体失活分析之间存在密切相关性。总之，我们的数据提供了证据，表明双侧、复发性和转移性甲状腺乳头状癌通常起源于单个克隆，甲状腺内转移可能在双侧肿瘤的发生以及这种恶性肿瘤的复发中发挥重要作用。
