Cytoplasmic p27 Expression is an Independent Prognostic Factor in Ovarian Cancer
Cytoplasmic p27 Expression is an Independent Prognostic Factor in Ovarian Cancer
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DOI：
10.1097/pgp.0b013e3181b64ec3
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发表时间：
2010-01-01
影响因子：
2.4
通讯作者：
Durrant, Lindy G.
中科院分区：
文献类型：
--
作者：
Duncan, Timothy J.;Al-Attar, Ahmad;Durrant, Lindy G.
细胞周期失调是癌症发生的重要先决条件。 p27 在细胞周期控制中具有明确的作用，因此在癌发生过程中可能会被破坏。 p27 表达（包括其亚细胞位置）对卵巢癌肿瘤行为的影响一直存在争议。本研究的目的是评估大量卵巢癌患者中 p27 的表达，并将其与包括总生存期在内的临床病理变量相关联。使用 339 个原发性卵巢癌的组织微阵列，通过免疫组织化学方法评估 p27 的表达。结合临床病理变量的综合数据库，研究了其对这些因素和生存的影响。细胞质 p27 对总生存期显示出渐进的负面影响 (P=0.004)。显示核 p27 的肿瘤预后也较差 (P=0.014)。相互独立预测预后的因素包括年龄、分期和术后是否存在肉眼可见的疾病。多变量分析表明，细胞质 p27 表达（而非细胞核）可独立预测预后（P = 0.042）。与粘液亚型相比，p27 表达的两个亚细胞位置在浆液亚型中更常见。细胞质 p27 独立预测卵巢癌较差的预后。当考虑到 p27 的抗增殖作用时，这些结果似乎违反直觉，但可能反映了 p27 在细胞周期调节中更复杂的功能。这些数据支持 p27 在细胞质中的新作用，可能是通过影响细胞凋亡、细胞运动和耐药性。
Dysregulation of the cell cycle is an important prerequisite for cancer development. p27 has an established role in cell cycle control and hence may be disrupted during carcinogenesis. The influence of p27 expression, including its subcellular location, on tumor behavior in ovarian cancer has been controversial. The purpose of this study was to evaluate the expression of p27 in a large population of patients with ovarian cancer and correlate this to clinicopathologic variables including overall survival. Using a tissue microarray of 339 primary ovarian cancers, the expression of p27 was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors and survival was studied. Cytoplasmic p27 showed a progressively negative impact on overall survival (P=0.004). Tumors displaying nuclear p27 also had poorer prognosis (P=0.014). Factors shown to predict prognosis independently of each other were age, stage, and the absence of macroscopic disease after surgery. Cytoplasmic p27 expression, but not nuclear, was independently predictive of prognosis on multivariate analysis (P = 0.042). Both subcellular locations of p27 expression were more frequently observed in serous compared with mucinous subtypes. Cytoplasmic p27 independently predicts poorer prognosis in ovarian carcinoma. These results seem counterintuitive, when considering the antiproliferative role of p27, but may reflect a more complex function of p27 within cell cycle regulation. These data support a novel role for p27 within the cytoplasm, possibly through effects on apoptosis, cellular motility, and drug resistance.