根据甲状腺外侵犯程度对甲状腺癌的分子、形态和预后分析。
Molecular, morphologic, and outcome analysis of thyroid carcinomas according to degree of extrathyroid extension.
机构信息
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA.
出版信息
Thyroid. 2010 Oct;20(10):1085-93. doi: 10.1089/thy.2010.0174.
BACKGROUND
The impact of varying degrees of extrathyroid extension (ETE), especially microscopic ETE (METE), on survival in thyroid carcinomas (TC) has not been well established. Our objective was to analyze ETE at the molecular and histologic levels and assess the effect of its extent on outcome.
METHODS
All cases of TC with ETE but without nodal metastases at presentation (NMP) were identified over a 20-year period and grouped into gross and METE. Twelve papillary thyroid carcinomas (PTCs) without ETE and NMP were also analyzed. Cases with paraffin tissues were subjected to mass spectrometry genotyping encompassing the most significant oncogenes in TC: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, and AKT1, and other related genes were surveyed.
RESULTS
Eighty-one (10%) of 829 patients in the database had ETE and no NMP. There was a much higher frequency of poorly differentiated and anaplastic carcinomas (12/29, 41%) in patients with gross ETE than in those with METE (3/52, 6%) (p < 0.01). There was a higher disease-specific survival (DSS) in patients with METE than in those with gross ETE (p < 0.0001). Except for an anaplastic case, no recurrences were detected in 45 patients with METE, including 23 PTC patients followed up for a median of 10 years without radioactive iodine therapy. Within patients with gross invasion into trachea/esophagus, tumors with high mitotic activity and/or tumor necrosis correlated with worse DSS (p < 0.05). Fifty-six cases with ETE were genotyped as follows: BRAFV600E, 39 (70%); BRAFV600E-AKT1, 1 (1.8%); NRAS, 1 (1.8%); KRAS, 1 (1.8%); RET/PTC, 3 (5%); wild type, 11 (19.6%). Within PTCs, BRAF positivity rate increased the risk of ETE (p = 0.01). If PTC follicular variants are excluded, BRAF positivity does not correlate with ETE status within classical/tall cell PTC.
CONCLUSION
(i) PTCs with METE without NMP have an extremely low recurrence rate in contrast to tumors with gross ETE. (ii) High mitotic activity and/or tumor necrosis confers worse DSS even in patients stratified for gross ETE in trachea/esophagus. (iii) BRAF positivity correlates with the presence of ETE in PTC, but this relationship is lost within classical/tall cell PTC if follicular variants are excluded from the analysis.
背景
甲状腺癌（TC）中不同程度的甲状腺外侵犯（ETE），尤其是微小甲状腺外侵犯（METE），对生存的影响尚未得到充分证实。我们的目的是分析分子和组织学水平的 ETE，并评估其程度对结局的影响。
方法
在 20 年的时间里，我们确定了所有在初诊时存在 ETE 但无淋巴结转移（NMP）的 TC 病例，并将其分为大体侵犯和 METE。还分析了 12 例无 ETE 和 NMP 的甲状腺乳头状癌（PTC）。对有石蜡组织的病例进行了涵盖 TC 中最重要的致癌基因的质谱基因分型：RET、BRAF、NRAS、HRAS、KRAS、PIK3CA 和 AKT1 的 111 个突变，以及其他相关基因的检测。
结果
数据库中 829 例患者中有 81 例（10%）存在 ETE 且无 NMP。与 METE 患者相比，大体侵犯患者中分化不良和间变癌的发生率更高（12/29，41%）与 METE 患者（3/52，6%）（p<0.01）。METE 患者的疾病特异性生存率（DSS）明显高于大体侵犯患者（p<0.0001）。在 45 例 METE 患者中，除了一例间变癌外，均未发现复发，包括 23 例 PTC 患者在中位随访 10 年后未接受放射性碘治疗。在大体侵犯气管/食管的患者中，高有丝分裂活性和/或肿瘤坏死与较差的 DSS 相关（p<0.05）。56 例 ETE 患者的基因型如下：BRAFV600E，39 例（70%）；BRAFV600E-AKT1，1 例（1.8%）；NRAS，1 例（1.8%）；KRAS，1 例（1.8%）；RET/PTC，3 例（5%）；野生型，11 例（19.6%）。在 PTC 中，BRAF 阳性率增加了 ETE 的风险（p=0.01）。如果排除滤泡变异型 PTC，BRAF 阳性与经典/高细胞 PTC 中的 ETE 状态无关。
结论
（i）与大体侵犯 ETE 相比，无 NMP 的 METE 伴 PTC 具有极低的复发率。（ii）即使在气管/食管大体侵犯患者中，高有丝分裂活性和/或肿瘤坏死也会导致较差的 DSS。（iii）BRAF 阳性与 PTC 中的 ETE 存在相关，但如果排除滤泡变异型，在经典/高细胞 PTC 中这种关系就会丢失。
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