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Maspin的表达及定位对卵巢癌血管生成和预后的影响。

Maspin expression and localization impact on angiogenesis and prognosis in ovarian cancer.

作者信息

Solomon L A, Munkarah A R, Schimp V L, Arabi M H, Morris R T, Nassar H, Ali-Fehmi R

机构信息

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wayne State University, Karmanos Cancer Institute, Harper Professional Building, 4160 John R St., Suite 2127, Detroit, MI 48201, USA.

出版信息

Gynecol Oncol. 2006 Jun;101(3):385-9. doi: 10.1016/j.ygyno.2005.11.049. Epub 2006 Jan 27.

Abstract

INTRODUCTION

The goal of this study is to evaluate the relation of maspin expression and its cellular localization to markers of angiogenesis in epithelial ovarian serous carcinoma (OSC).

MATERIALS AND METHODS

We identified 118 patients with high-grade advanced stage OSC who were treated at our institution. Clinical data were collected, and immunohistochemistry (IHC) with antibodies to VEGF, CD34, COX-2, and maspin was performed on paraffin-embedded tumor blocks. CD34 immunostaining was used to determine microvessel density. The correlation between the various molecular markers was assessed using the Chi-square test. Survival analysis was computed using the Kaplan-Meier model, and various prognostic variables were compared using Cox regression analysis.

RESULTS

Maspin expression was noted in 81.4% (96/118) of tumors. Expression was localized to the nuclear compartment in 21.2% of cases, whereas 60.2% of cases showed evidence of cytoplasmic +/- nuclear expression. Tumors that exhibited nuclear maspin expression had lower VEGF and COX-2 expression than tumors with negative or cytoplasmic expression. Tumors with high nuclear maspin expression had lower mean MVD than those with low or negative expression. The median survival based on localization of maspin was 1146 days for those with negative tumors, 1803 days for those with nuclear maspin, and 637 days for those with cytoplasmic maspin (P < 0.001). In a Cox regression analysis, maspin localization was an independent prognostic factor.

CONCLUSION

Maspin expression and localization seem to play a role in ovarian cancer angiogenesis and progression. High nuclear expression was associated with reduced markers of angiogenesis and prolonged survival.

摘要

引言

本研究的目的是评估在卵巢上皮性浆液性癌(OSC)中,乳腺丝抑蛋白(maspin)的表达及其细胞定位与血管生成标志物之间的关系。

材料与方法

我们纳入了在本机构接受治疗的118例高级别晚期OSC患者。收集临床数据,并对石蜡包埋的肿瘤组织块进行针对血管内皮生长因子(VEGF)、CD34、环氧合酶-2(COX-2)和maspin的免疫组织化学(IHC)检测。采用CD34免疫染色来确定微血管密度。使用卡方检验评估各种分子标志物之间的相关性。采用Kaplan-Meier模型进行生存分析,并使用Cox回归分析比较各种预后变量。

结果

在81.4%(96/118)的肿瘤中检测到maspin表达。21.2%的病例中表达定位于细胞核,而60.2%的病例显示有细胞质±细胞核表达的证据。与阴性或细胞质表达的肿瘤相比,细胞核maspin表达的肿瘤VEGF和COX-2表达较低。细胞核maspin高表达的肿瘤平均微血管密度低于低表达或阴性表达的肿瘤。根据maspin定位,阴性肿瘤患者的中位生存期为1146天,细胞核maspin患者为1803天,细胞质maspin患者为637天(P<0.001)。在Cox回归分析中,maspin定位是一个独立的预后因素。

结论

maspin的表达和定位似乎在卵巢癌血管生成和进展中起作用。高细胞核表达与血管生成标志物减少和生存期延长相关。

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