Aust Stefanie, Pils Sophie, Polterauer Stefan, Horvat Reinhard, Cacsire Castillo-Tong Dan, Pils Dietmar, Dudek Grazyna, Schmid Bernd, Speiser Paul, Reinthaller Alexander, Grimm Christoph
Departments of *Gynaecology and Gynaecological Oncology, Comprehensive Cancer Center †Pathology, Medical University of Vienna ‡Department of Gynaecology and Gynaecological Oncology, Hietzing Hospital, Vienna, Austria.
Appl Immunohistochem Mol Morphol. 2013 Dec;21(6):518-24. doi: 10.1097/PAI.0b013e318284a053.
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.
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。
