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甲状腺微小乳头状癌及其配对淋巴结转移灶中的BRAF V600E突变与p27 kip1表达

BRAF V600E mutation and p27 kip1 expression in papillary carcinomas of the thyroid <or=1 cm and their paired lymph node metastases.

作者信息

Rodolico Vito, Cabibi Daniela, Pizzolanti Giuseppe, Richiusa Pierina, Gebbia Nicola, Martorana Anna, Russo Antonio, Amato Marco C, Galluzzo Aldo, Giordano Carla

机构信息

Department of Human Pathology, University of Palermo, Palermo, Italy.

出版信息

Cancer. 2007 Sep 15;110(6):1218-26. doi: 10.1002/cncr.22912.

Abstract

BACKGROUND

BRAF(V600E) mutation and p27(kip1) expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas.

METHODS

Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) <or=1 cm were analyzed for BRAF(V600E) mutation by a real-time, allele-specific amplification and for p27(kip1) expression by immunohistochemistry.

RESULTS

The BRAF(V600E) mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAF(V600E) mutation was significantly higher than that of patients without mutations. A significant association was found between low p27(Kip1) protein expression and multifocality, bilaterality, and extrathyroidal extension, in addition to LN metastasis. In 42 cases with LN metastases, 23 harbored the BRAF(V600E) mutation in the metastatic tumor and presented a wider diameter of the largest metastatic area, a higher number of involved LNs, and a higher percentage of metastatic lesions with extracapsular extension of LN (ECE-LN). A significantly lower mean value of p27(Kip1) was observed in LNs harboring the BRAF(V600E) mutation and in ECE-LN; an inverse correlation was found between p27(Kip1) and the number of metastatic LNs, as well as the diameter of the largest metastatic area in LN.

CONCLUSIONS

The authors' data suggested that BRAF(V600E) mutation and p27(Kip1) down-regulation in cancer cells of PTC <or=1 cm may be factors that facilitate tumor-cell growth and progression once these are seeded in the LNs.

摘要

背景

BRAF(V600E)突变和p27(kip1)表达已被作为可能预测不同肿瘤以及甲状腺乳头状癌预后的新指标。

方法

对214例接受全甲状腺或近全甲状腺切除术且组织学诊断为直径≤1 cm甲状腺乳头状癌(PTC)的连续患者的组织样本进行分析,采用实时等位基因特异性扩增法检测BRAF(V600E)突变,采用免疫组织化学法检测p27(kip1)表达。

结果

在所检测的肿瘤中,88例检测到BRAF(V600E)突变,有淋巴结(LN)转移组和无转移组之间存在显著差异;BRAF(V600E)突变患者的平均年龄显著高于无突变患者。除LN转移外,还发现低p27(Kip1)蛋白表达与多灶性、双侧性和甲状腺外侵犯之间存在显著关联。在42例有LN转移的病例中,23例转移瘤中存在BRAF(V600E)突变,且最大转移灶直径更大、受累LN数量更多、LN包膜外扩展(ECE-LN)的转移灶百分比更高。在存在BRAF(V600E)突变的LN和ECE-LN中,观察到p27(Kip1)的平均价值显著较低;发现p27(Kip1)与转移LN数量以及LN中最大转移灶直径呈负相关。

结论

作者的数据表明,直径≤1 cm的PTC癌细胞中的BRAF(V600E)突变和p27(Kip1)下调可能是一旦肿瘤细胞种植于LN中便促进其生长和进展的因素。

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