Vermehren-Schmaedick Anke, Mhawech-Fauceglia Paulette, Park Byung S, Pejovic Tanja, Luoh Shiuh-Wen
Hospital & Specialty Medicine, VA Portland Health Care System, Portland, OR, USA.
Translational Oncology Program, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Oncotarget. 2020 Jun 16;11(24):2273-2289. doi: 10.18632/oncotarget.27593.
To study GRB7 protein expression in normal human tissues and breast and ovarian cancers, and determine its clinical significance. GRB7 protein was expressed in multiple tissues, including myoepithelial cells of normal breast and fibroadenoma. Cytoplasmic GRB7 expression was seen predominantly in HER-2 positive and, to a lesser extent, triple negative breast cancer. Membrane localization of GRB7 was present in a subset of breast cancers with high cytoplasmic GRB7 expression. Univariate and multivariate analysis found that cytoplasmic GRB7 expression was associated with a negative progesterone receptor status, while membrane GRB7 expression was associated with a negative axillary nodal status. Membrane associated GRB7 expression was present in a subset of ovarian cancers with high cytoplasmic GRB7 expression. Membrane GRB7 expression displayed a trend towards improved recurrence free survival (RFS). Landmark analysis suggested an RFS advantage for ovarian cancers that had GRB7 membrane expression and survived beyond 27 months; GRB7 membrane expression in two or more cores (out of three) predicted an improved RFS. Membrane expression of GRB7 protein was observed in breast cancer cell lines with high GRB7 protein expression . GRB7 protein membrane expression may be associated with a better prognosis in breast and ovarian cancers. The favorable prognostic value of GRB7 protein membrane expression and its underlying mechanism is worthy of further investigation. Immunohistochemistry of normal human tissues, breast tissues of various pathologies, and clinically annotated ovarian cancers was performed to correlate the patterns of GRB7 expression with biomarkers or clinical outcome.
研究GRB7蛋白在正常人体组织、乳腺癌和卵巢癌中的表达情况，并确定其临床意义。GRB7蛋白在多种组织中表达，包括正常乳腺的肌上皮细胞和纤维腺瘤。细胞质GRB7表达主要见于HER-2阳性乳腺癌，在三阴性乳腺癌中表达程度较低。GRB7的膜定位存在于细胞质GRB7高表达的一部分乳腺癌中。单因素和多因素分析发现，细胞质GRB7表达与孕激素受体阴性状态相关，而膜GRB7表达与腋窝淋巴结阴性状态相关。膜相关GRB7表达存在于细胞质GRB7高表达的一部分卵巢癌中。膜GRB7表达显示出无复发生存期（RFS）改善的趋势。标志性分析表明，GRB7膜表达且生存超过27个月的卵巢癌具有RFS优势；三个核心中有两个或更多核心出现GRB7膜表达预示着RFS改善。在GRB7蛋白高表达的乳腺癌细胞系中观察到GRB7蛋白的膜表达。GRB7蛋白的膜表达可能与乳腺癌和卵巢癌的较好预后相关。GRB7蛋白膜表达的良好预后价值及其潜在机制值得进一步研究。对正常人体组织、各种病理类型的乳腺组织以及有临床注释的卵巢癌进行免疫组织化学检测，以将GRB7表达模式与生物标志物或临床结果相关联。
