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mTOR 蛋白的表达及其在子宫内膜癌中的临床意义。

Expression of mTOR protein and its clinical significance in endometrial cancer.

机构信息

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Med Sci Monit. 2009 Oct;15(10):BR301-305.

Abstract

BACKGROUND

Mammalian target of rapamycin (mTOR) plays a crucial role in carcinogenesis by regulating protein synthesis, and mTOR inhibitors have been identified as potential anticancer agents in various cancers. Since the most common genetic change in endometrial cancer is the mutation of phosphatase and tensin homologue (PTEN), a negative regulator of mTOR, we evaluated mTOR expression in endometrial cancer and its relationship with other clinicopathological characteristics and expression patterns of cyclooxygenase-2 (COX-2) and p53.

MATERIAL/METHODS: Immunohistochemical analysis of mTOR was performed on paraffin-embedded tissue specimens obtained from 141 patients with endometrial carcinoma. Results were correlated with the clinicopathological characteristics and expression pattern of COX-2 and p53.

RESULTS

mTOR overexpression was detected in 7.1% (10/141) of patients. mTOR expression was highly correlated with old age, menopausal status and COX-2 expression (P<0.05). Multivariate analysis revealed that COX-2 was the only independent factor related to expression of mTOR. However, there was no correlation of mTOR expression with prognostic factors such as histologic type, grade, invasion of myometrium, lymph node metastasis, stage, and survival.

CONCLUSIONS

Our findings suggest that the expression of mTOR is infrequent and is associated with COX-2 overexpression. Careful selection of patients might be necessary in the use of mTOR inhibitor as a molecular targeted therapy for patients with endometrial cancer.

摘要

背景

哺乳动物雷帕霉素靶蛋白(mTOR)通过调节蛋白质合成在致癌作用中发挥关键作用,并且已经发现 mTOR 抑制剂是各种癌症中的潜在抗癌剂。由于子宫内膜癌中最常见的遗传变化是磷酸酶和张力蛋白同源物(PTEN)的突变,mTOR 的负调节剂,我们评估了 mTOR 在子宫内膜癌中的表达及其与其他临床病理特征以及环氧化酶-2(COX-2)和 p53 的表达模式的关系。

材料/方法:对 141 例子宫内膜癌患者的石蜡包埋组织标本进行 mTOR 的免疫组织化学分析。结果与 COX-2 和 p53 的表达模式与临床病理特征相关。

结果

在 7.1%(10/141)的患者中检测到 mTOR 过表达。mTOR 表达与年龄较大、绝经状态和 COX-2 表达高度相关(P<0.05)。多变量分析显示,COX-2 是与 mTOR 表达相关的唯一独立因素。然而,mTOR 表达与组织学类型、分级、肌层浸润、淋巴结转移、分期和生存等预后因素无相关性。

结论

我们的研究结果表明,mTOR 的表达不常见,并且与 COX-2 过表达相关。在将 mTOR 抑制剂作为子宫内膜癌的分子靶向治疗药物使用时,可能需要仔细选择患者。

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