The prognostic significance of GRB7 protein expression and localization in human breast and ovarian cancers
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Anke Vermehren-Schmaedick1,2,3, Paulette Mhawech-Fauceglia4, Byung S. Park5,6, Tanja Pejovic2,7,* and Shiuh-Wen Luoh1,2,3,*
1 Hospital & Specialty Medicine, VA Portland Health Care System, Portland, OR, USA
2 Translational Oncology Program, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
3 Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
4 Department of Anatomic Pathology, Aurora Diagnostics/Sonic Healthcare, Las Vegas, NV, USA
5 Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
6 School of Public Health, Oregon Health & Science University - Portland State University, Portland, OR, USA
7 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA
* These authors contributed equally to this work
Keywords: GRB7 expression; breast cancer; ovarian cancer; immunohistochemistry; prognosis
Received: March 04, 2020 Accepted: April 14, 2020 Published: June 16, 2020
Objective: To study GRB7 protein expression in normal human tissues and breast and ovarian cancers, and determine its clinical significance.
Results: 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 in vitro.
Conclusion: 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.
Methods: 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.
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