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γH2AX在甲状腺乳头状癌和结节性甲状腺肿中的差异表达。

Disparity expression of gammaH2AX in papillary thyroid cancer and nodular goiter.

作者信息

Hu Sisi, Zhang Gu, Xu Jiajie, Zhu Xin, Lu Xiaoxiao, Jiang Liehao, Wang Qingliang, Hou Xiuxiu, Cao Jun, Ge Minghua

出版信息

Clin Lab. 2014;60(12):2031-7. doi: 10.7754/clin.lab.2014.140603.

Abstract

BACKGROUND

H2AX, one of the variants of histone H2A with conserved sequence, plays a vital role in maintaining genomic stability. DNA double-strand break (DSB) induces H2AX phosphorylation (γH2AX). Growing evidence indicated γH2AX was linked to thyroid disease. However, the precise expression of γH2AX in papillary thyroid carcinoma (PTC) and nodular goiter was unknown. In this study, the yH2AX expression in PTC and nodular goiter and the significance of the aberrant expression were investigated.

METHODS

The γH2AX expression level was evaluated by immunohistochemistry staining in 140 specimens with thyroid diseases (30 cases of nodular goiter, 30 cases of PTC, and 80 cases of PTC coexisting with nodular goiter). The possible relationships between γH2AX expression and patients' clinicopathological characteristics were analyzed.

RESULTS

In the set of nodular goiter, 20.0% (6/30) of nodular goiter component and 10.0% (3/30) of normal adjacent tissues exhibited high expression of γH2AX (p > 0.05). In the set of PTC, 70.0% (21/30) of PTC component and 0.0% (0/30) of normal adjacent tissues showed high expression of γH2AX (p < 0.05). In the set of PTC coexisting with nodular goiter, 95.0% (76/80) of PTC component, 12.5% (10/80) of nodular goiter component, and 8.8% (7/80) of normal adjacent specimens showed high expression of γH2AX (p < 0.05). 85.5% (65/76) of PTC patients with lymph node metastasis were found to have a high expression level of γH2AX, and the proportion was lower than that in patients without lymph node metastasis (34/34, 100.0%) (p = 0.003). High γH2AX expression was also found in 76.2% (16/21) of stage IV patients and the proportion was lower than that in stage I - III patients (83/89, 93.3%) (p = 0.034). No statistically significant correlation was found between yH2AX expression level and other clinicopathological features, including age, gender, capsular invasion, tumor size, tumor focus number, distant metastasis, and T status.

CONCLUSIONS

γH2AX expression was increased in PTC patients, while nodular goiter and normal adjacent tissues exhibited no statistically significant difference in γH2AX expression. yH2AX expression had a negative correlation with TNM stage and lymph node metastasis. γH2AX seems to play a more critical role in early-stage PTC rather than late-stage PTC and might inhibit lymph node metastasis.

摘要

背景

H2AX是组蛋白H2A的一种变体,其序列保守,在维持基因组稳定性方面发挥着至关重要的作用。DNA双链断裂(DSB)可诱导H2AX磷酸化(γH2AX)。越来越多的证据表明γH2AX与甲状腺疾病有关。然而,γH2AX在甲状腺乳头状癌(PTC)和结节性甲状腺肿中的精确表达尚不清楚。在本研究中,对PTC和结节性甲状腺肿中γH2AX的表达及其异常表达的意义进行了研究。

方法

采用免疫组织化学染色法评估140例甲状腺疾病标本(30例结节性甲状腺肿、30例PTC以及80例PTC合并结节性甲状腺肿)中γH2AX的表达水平。分析γH2AX表达与患者临床病理特征之间的可能关系。

结果

在结节性甲状腺肿组中,20.0%(6/30)的结节性甲状腺肿成分和10.0%(3/30)的相邻正常组织γH2AX呈高表达(p>0.05)。在PTC组中,70.0%(21/30)的PTC成分和0.0%(0/30)的相邻正常组织γH2AX呈高表达(p<0.05)。在PTC合并结节性甲状腺肿组中,95.0%(76/80)的PTC成分、12.5%(10/80)的结节性甲状腺肿成分以及8.8%(7/80)的相邻正常标本γH2AX呈高表达(p<0.05)。发现85.5%(65/76)有淋巴结转移的PTC患者γH2AX表达水平高,该比例低于无淋巴结转移患者(34/34,100.0%)(p=0.003)。IV期患者中也有76.2%(16/21)γH2AX表达高,该比例低于I - III期患者(83/89,93.3%)(p=0.034)。未发现γH2AX表达水平与其他临床病理特征(包括年龄、性别、包膜侵犯、肿瘤大小、肿瘤灶数量、远处转移和T分期)之间存在统计学显著相关性。

结论

PTC患者γH·2AX表达增加,而结节性甲状腺肿及其相邻正常组织γH2AX表达无统计学显著差异。γH2AX表达与TNM分期和淋巴结转移呈负相关。γH2AX似乎在早期PTC中比晚期PTC发挥更关键的作用,可能抑制淋巴结转移。

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