Peng Wen-Ting, Hu Xin, Yao Ling, Jiang Yi-Zhou, Shao Zhi-Ming
Department of Breast Surgery, Shanghai Cancer Center and Cancer Institute, Fudan University, Shanghai, China.
Ann Surg Oncol. 2014 Dec;21 Suppl 4:S648-56. doi: 10.1245/s10434-014-3746-y. Epub 2014 May 3.
Girdin was identified as a novel Akt substrate that contributes to a positive feedback loop between Girdin and Akt. Although several recent studies have demonstrated that Girdin is involved in tumor metastasis, the clinical implications of Girdin in breast cancer remain unclear.
To retrospectively evaluate the prognostic value of Girdin in breast cancer, we performed an immunohistochemistry screening for Girdin using tissue microarrays constructed from 250 patients who were histologically confirmed as having invasive ductal breast carcinoma at the Fudan University Shanghai Cancer Center.
Our results demonstrated that the levels of Girdin in different subcellular distributions, including Girdin in the nucleus (GN) and the cytoplasm (GC) were each associated with the clinical parameters of breast cancer, including phospho-Akt (S473) [p = 0.014 for GN], phospho-Akt (T308) [p = 0.045 for GC], estrogen receptor (ER) [p = 0.012 for GN and p = 0.004 for GC], progesterone receptor (p = 0.028 for GC) and human epidermal growth factor receptor 2 status (p = 0.004 for GC). Moreover, we showed that elevated expression of GN indicated a worse disease-free survival (p = 0.032) and overall survival (p = 0.011) exclusively in the ER-positive breast cancer population.
Cumulatively, our findings suggest that GN might serve as an important prognostic factor for ER-positive breast carcinoma.
Girdin被鉴定为一种新型的Akt底物，它有助于Girdin与Akt之间形成正反馈回路。尽管最近的几项研究表明Girdin参与肿瘤转移，但Girdin在乳腺癌中的临床意义仍不清楚。
为了回顾性评估Girdin在乳腺癌中的预后价值，我们使用由复旦大学附属肿瘤医院250例经组织学确诊为浸润性导管癌患者构建的组织芯片对Girdin进行免疫组织化学筛查。
我们的结果表明，不同亚细胞分布中的Girdin水平，包括细胞核中的Girdin（GN）和细胞质中的Girdin（GC），均与乳腺癌的临床参数相关，包括磷酸化Akt（S473）[GN，p = 0.014]、磷酸化Akt（T308）[GC，p = 0.045]、雌激素受体（ER）[GN，p = 0.012；GC，p = 0.004]、孕激素受体（GC，p = 0.028）和人表皮生长因子受体2状态（GC，p = 0.004）。此外，我们发现GN表达升高仅在雌激素受体阳性乳腺癌人群中提示无病生存期较差（p = 0.032）和总生存期较差（p = 0.011）。
总体而言，我们的研究结果表明GN可能是雌激素受体阳性乳腺癌的一个重要预后因素。
