PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma.
PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma.
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DOI：
10.1038/bjc.2015.169
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发表时间：
2015-06-09
影响因子：
8.8
通讯作者：
Al-Kuraya KS
中科院分区：
文献类型：
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作者：
Beg S;Siraj AK;Jehan Z;Prabakaran S;Al-Sobhi SS;Al-Dawish M;Al-Dayel F;Al-Kuraya KS
位于染色体10q23.3上的PTEN基因是一种肿瘤抑制基因，在许多类型的人类癌症中失活。已知的PTEN失活机制是突变、异常甲基化引起的表观遗传沉默或基因缺失。虽然PTEN的作用已被证明在许多癌症中，在甲状腺乳头状癌（PTC）的PTEN的改变尚未完全阐明。本研究的目的是通过免疫组化和荧光原位杂交（FISH）全面研究中东甲状腺乳头状癌中PTEN的改变。通过组织微阵列（TMA）格式的免疫组织化学分析了1000多例甲状腺乳头状癌患者的PTEN蛋白表达。通过FISH分析PTEN拷贝数变化，并将数据与临床病理参数沿着生存分析。在24.5%的PTC样品中观察到完全不存在染色所反映的PTEN失活，而通过FISH仅在4.8%的测试样品中观察到PTEN缺失。PTEN蛋白表达缺失与PTEN基因缺失之间无相关性。然而，有趣的是，PTEN表达缺失与甲状腺乳头状癌的滤泡变异亚型显著相关。我们的研究证实，PTEN可能在PTC的发病机制中发挥作用。PTEN蛋白表达缺失在滤泡型甲状腺乳头状癌中更为常见。PTEN蛋白表达缺失与基因缺失之间缺乏相关性可能表明基因缺失可能不是导致PTEN表达缺失的唯一原因，这些结果可能提高了其他机制如启动子甲基化介导的基因沉默负责PTEN失活的可能性。
PTEN gene at chromosomes 10q23.3 is a tumour suppressor gene that is inactivated in many types of human cancers. The known mechanisms of PTEN inactivation are rendered to mutation, epigenetic silencing by aberrant methylation or gene deletion. Although PTEN role has been documented in many cancers, PTEN alteration in papillary thyroid carcinoma (PTC) has not been fully elucidated. The aim of this study is to comprehensively investigate PTEN alterations in a large cohort of Middle Eastern papillary thyroid cancer by immunohistochemistry and fluorescent in situ hybridisation (FISH). PTEN protein expression was analysed by immunohistochemistry in a tissue microarray (TMA) format in a large cohort of more than 1000 patients with papillary thyroid cancer. Copy number changes in PTEN were analysed by FISH and data were correlated with clinicopathological parameters along with survival analysis. PTEN inactivation reflected by complete absence of staining was seen in 24.5% of PTC samples, whereas PTEN deletion was seen only in 4.8% of the tested samples by FISH. No association was seen between PTEN loss of protein expression and PTEN gene deletion. However, interestingly, PTEN loss of expression was significantly associated with the follicular variant subset of papillary thyroid cancer. Our study confirmed that PTEN might have a role in pathogenesis in a subset of PTC. PTEN loss of protein expression is a more common event in follicular variant of papillary thyroid cancer. Lack of association between PTEN loss of protein expression and PTEN gene deletion might indicate that gene deletion may not be the sole cause for PTEN loss of expression and these results might raise the possibility of other mechanism such as promoter methylation-mediated gene silencing to be responsible for PTEN inactivation.