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PTEN、PI3K、MTOR和KRAS表达的评估及其与分化型甲状腺癌的临床和预后相关性

Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma.

作者信息

Duman Berna B, Kara Oğuz I, Uğuz Aysum, Ates Berna T

机构信息

Department of Medical Oncology, Medical Faculty, Cukurova University, Adana, Turkey.

Department of Pathology, Medical Faculty, Cukurova University, Adana, Turkey.

出版信息

Contemp Oncol (Pozn). 2014;18(4):234-40. doi: 10.5114/wo.2014.43803. Epub 2014 Jul 4.

DOI:10.5114/wo.2014.43803
PMID:25258580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4171472/
Abstract

AIM OF THE STUDY

Important signalling pathways play fundamental roles in the pathogenesis of thyroid carcinoma (TC). PTEN, mTOR, PI3K-p85 and K-Ras are the principal factors involved in these signalling pathways. To immunohistochemically examine the expressions of PI3K, mTOR and PTEN in patients suffering from follicular TC, papillary TC or variants thereof, as well as to investigate KRAS mutations via PCR to determine their clinical and prognostic relevance to differentiated thyroid cancer.

MATERIAL AND METHODS

The expression of PTEN, PI3K-p85 and mTOR was immunohistochemically examined, and the mutation of K-Ras was examined via PCR. The results obtained were compared to the clinico-pathologic characteristics of the patients.

RESULTS

A significant correlation was found between p85 expression and lymphovascular invasions and between PTEN expression and multifocality (p = 0.048 and p = 0.04, respectively), and a correlation between p85 and capsular invasion was found, with a borderline statistical significance (p = 0.056). No expression of PTEN, p85 or Mtor was detected in normal tissue. K-Ras mutation was examined in 66 of the 101 patients (57.4%), and the percentage of patients exhibiting a K-Ras mutation was 17.4%. All of the patients exhibiting a K-Ras mutation were women (p = 0.047). The disease-free survival was 44.6 months (95% CI: 37.9-51.3) and was statistically significantly higher in the group that displayed level 1 or lower expression of p85 (p = 0.043).

CONCLUSIONS

The expression levels of the aforementioned markers were significantly higher in TC cells than in normal tissue. A significant correlation was detected between K-Ras mutation and gender. This study demonstrates that p85 and PTEN are markers that should be evaluated in further studies of TC.

摘要

研究目的

重要的信号通路在甲状腺癌(TC)的发病机制中起重要作用。PTEN、mTOR、PI3K-p85和K-Ras是这些信号通路中的主要因素。通过免疫组织化学检测滤泡性TC、乳头状TC或其变体患者中PI3K、mTOR和PTEN的表达,并通过PCR研究KRAS突变,以确定它们与分化型甲状腺癌的临床和预后相关性。

材料与方法

采用免疫组织化学检测PTEN、PI3K-p85和mTOR的表达,并通过PCR检测K-Ras的突变。将所得结果与患者的临床病理特征进行比较。

结果

发现p85表达与淋巴管侵犯之间以及PTEN表达与多灶性之间存在显著相关性(分别为p = 0.048和p = 0.04),并且发现p85与包膜侵犯之间存在相关性,具有临界统计学意义(p = 0.056)。在正常组织中未检测到PTEN、p85或Mtor的表达。在101例患者中的66例(57.4%)检测了K-Ras突变,出现K-Ras突变的患者百分比为17.4%。所有出现K-Ras突变的患者均为女性(p = 0.047)。无病生存期为44.6个月(95%CI:37.9 - 51.3),在p85表达水平为1级或更低的组中显著更高(p = 0.043)。

结论

上述标志物在TC细胞中的表达水平显著高于正常组织。检测到K-Ras突变与性别之间存在显著相关性。本研究表明,p85和PTEN是在TC进一步研究中应评估的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67b6/4171472/78d108653003/WO-18-23045-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67b6/4171472/78d108653003/WO-18-23045-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67b6/4171472/c63f88cfac1d/WO-18-23045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67b6/4171472/04bea7e07a28/WO-18-23045-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67b6/4171472/1717aa202723/WO-18-23045-g005.jpg
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