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Bcl-2及抗凋亡BAG家族蛋白在卵巢癌中的表达

Expression of Bcl-2 and the antiapoptotic BAG family proteins in ovarian cancer.

作者信息

Aust Stefanie, Pils Sophie, Polterauer Stefan, Horvat Reinhard, Cacsire Castillo-Tong Dan, Pils Dietmar, Dudek Grazyna, Schmid Bernd, Speiser Paul, Reinthaller Alexander, Grimm Christoph

机构信息

Departments of *Gynaecology and Gynaecological Oncology, Comprehensive Cancer Center †Pathology, Medical University of Vienna ‡Department of Gynaecology and Gynaecological Oncology, Hietzing Hospital, Vienna, Austria.

出版信息

Appl Immunohistochem Mol Morphol. 2013 Dec;21(6):518-24. doi: 10.1097/PAI.0b013e318284a053.

Abstract

In epithelial ovarian cancer (EOC), literature on the prognostic value of B-cell lymphoma 2 (Bcl-2) is limited and inconsistent. Little is known about the expression patterns and the prognostic value of prosurvival proteins of the Bcl-2-associated athanogene (BAG) family proteins interacting with Bcl-2. The major aim of this study was to further define the expression pattern and the prognostic role of Bcl-2 together with BAG-1, BAG-3, and BAG-4 proteins in EOC patients receiving platinum/taxane-based chemotherapy. A tissue array was constructed comprising 63 EOC patients. The expression and the prognostic value of Bcl-2, BAG-1, BAG-3, and BAG-4 in EOC were evaluated by immunohistochemistry and multivariate analysis. A positive cytoplasmic staining for Bcl-2 was observed in 23.8% of EOC samples and in all histologic subtypes. BAG-1, BAG-3, and BAG-4 were detected in tumor cell nuclei and cytoplasm. Interestingly, all patients presenting with a positive Bcl-2 staining showed additional positive nuclear and cytoplasmic BAG-4 expression (P=0.014). Expression of Bcl-2, or the BAG family proteins, independent of nuclear or cytoplasmic localization, had no significant impact on either disease-free or overall survival, both in univariate and multivariate survival analyses with the limitation of a small cohort of cases. In this study, no association between Bcl-2 expression in EOC tumor tissue and prognosis was found. Similarly, nuclear and cytoplasmic expression of the prosurvival proteins of the BAG family had no significant impact on patients' outcome.

摘要

在上皮性卵巢癌(EOC)中,关于B细胞淋巴瘤2(Bcl-2)预后价值的文献有限且不一致。对于与Bcl-2相互作用的Bcl-2相关抗凋亡基因(BAG)家族蛋白的表达模式及其预后价值知之甚少。本研究的主要目的是进一步明确在接受铂类/紫杉烷类化疗的EOC患者中,Bcl-2与BAG-1、BAG-3和BAG-4蛋白的表达模式及其预后作用。构建了一个包含63例EOC患者的组织芯片。通过免疫组织化学和多变量分析评估Bcl-2、BAG-1、BAG-3和BAG-4在EOC中的表达及预后价值。在23.8%的EOC样本及所有组织学亚型中均观察到Bcl-2胞质染色阳性。在肿瘤细胞核和细胞质中检测到BAG-1、BAG-3和BAG-4。有趣的是,所有Bcl-2染色阳性患者均显示BAG-4核及胞质表达额外阳性(P = 0.014)。在单变量和多变量生存分析中,无论Bcl-2或BAG家族蛋白的表达,无论其在细胞核还是细胞质中的定位,对无病生存期或总生存期均无显著影响,但病例数较少存在局限性。在本研究中,未发现EOC肿瘤组织中Bcl-2表达与预后之间存在关联。同样,BAG家族抗生存蛋白的核及胞质表达对患者预后也无显著影响。

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