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子宫内膜癌中单一及联合生物标志物的临床意义和预后价值

Clinical implications and prognostic value of single and combined biomarkers in endometrial carcinoma.

作者信息

Li Mingzhu, Zhao Lijun, Shen Danhua, Li Xiaoping, Wang Jianliu, Wei Lihui

机构信息

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China. Email:

出版信息

Chin Med J (Engl). 2014;127(8):1459-63.

PMID:24762589
Abstract

BACKGROUND

Endometrial carcinoma is one of the most common gynecological cancers and the incidence has been increasing. This study was to identify the relationship of estrogen receptor (ER), progestrone receptor (PR), P53 protein, Ki-67 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) with endometrial carcinoma, the assessment of these biomarkers and their association with clinicopathological parameters was performed.

METHODS

A total of 198 cases of primary endometrial carcinoma were investigated for ER, PR, Ki-67, P53, and PTEN antigens by immunohistochemical methods. The association of these markers with age, menopause status, histological type, FIGO stage, grading, depth of invasion, lymph node involvement and serum tumor marker was examined.

RESULTS

The percentages of Ki-67- and P53-negative endometrial tumors were significantly higher in ER-positive compared with ER-negative tumors (both P = 0.000). The same trend was evident with PR status. The percentage of PTEN-positive tumors was significantly higher in PR-positive compared with PR-negative tumors (P = 0.021), but was no difference in tumors with different ER status. There was no clear association between PTEN positivity and clinicopathological parameters except more relevance with endometrioid histotype (P = 0.013). There was a statistically significant difference in the distribution of the different combined biological factors examined in disease-free survival.

CONCLUSIONS

ER and PR status were significant predictors with staging, grading and recurrence. P53 and Ki-67 expression were inversely correlated with both ER and PR expression and have more aggressive clinicopathological features. PTEN expression was inversely correlated with PR expression but not with ER expression. The combined type of ER+PR+P53-PTEN+ was in the majority in endometrial cancer and seemed to be related to better clinical outcome. The combination of ER-PR-P53+PTEN- represented the worst disease-free survival and was strongly associated with poorest survival rate.

摘要

背景

子宫内膜癌是最常见的妇科癌症之一,其发病率一直在上升。本研究旨在确定雌激素受体(ER)、孕激素受体(PR)、P53蛋白、Ki-67和第10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)与子宫内膜癌的关系,并对这些生物标志物进行评估及其与临床病理参数的相关性分析。

方法

采用免疫组织化学方法对198例原发性子宫内膜癌患者的ER、PR、Ki-67、P53和PTEN抗原进行检测。分析这些标志物与年龄、绝经状态、组织学类型、国际妇产科联盟(FIGO)分期、分级、浸润深度、淋巴结转移及血清肿瘤标志物的相关性。

结果

ER阳性的子宫内膜肿瘤中Ki-67和P53阴性的比例显著高于ER阴性肿瘤(均P = 0.000)。PR状态也呈现相同趋势。PR阳性肿瘤中PTEN阳性的比例显著高于PR阴性肿瘤(P = 0.021),但不同ER状态的肿瘤之间无差异。除了与子宫内膜样组织学类型相关性更强(P = 0.013)外,PTEN阳性与临床病理参数之间无明显关联。在无病生存期方面,所检测的不同联合生物学因素的分布存在统计学显著差异。

结论

ER和PR状态是分期、分级和复发的重要预测指标。P53和Ki-67的表达与ER和PR的表达呈负相关,且具有更具侵袭性的临床病理特征。PTEN的表达与PR表达呈负相关,但与ER表达无关。ER+PR+P53-PTEN+的联合类型在子宫内膜癌中占大多数,似乎与较好的临床结局相关。ER-PR-P53+PTEN-的联合类型代表最差的无病生存期,且与最低的生存率密切相关。

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