Cell surface GRP78: A potential marker of good prognosis and response to chemotherapy in breast cancer

Yerushalmi,Rinat; Raiter,Annat; Nalbandyan,Karen; Hardy,Britta

doi:10.3892/ol.2015.3579

Cell surface GRP78: A potential marker of good prognosis and response to chemotherapy in breast cancer

Authors:
- Rinat Yerushalmi
- Annat Raiter
- Karen Nalbandyan
- Britta Hardy
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Affiliations: Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel, Department of Pathology, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel
Published online on: August 6, 2015 https://doi.org/10.3892/ol.2015.3579
Pages: 2149-2155
Copyright: © Yerushalmi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The 78‑kDa glucose‑regulated protein (GRP78) is a stress induced heat shock protein which, under limiting conditions, functions as a cell surface signaling receptor. Tumor cells are considered to be subjected to a physiologically stressful microenvironment due to their excessive growth. The role of GRP78 in tumor survival has been of notable interest. The present study aimed to assess the potential prognostic and predictive value of cell surface GRP78 expression in breast cancer tumor cells. Cell surface and cytoplasmic expression of GRP78 was examined by immunohistochemical staining of GRP78 in breast cancer archival paraffin‑embedded tumor specimens. The cohort studied included breast cancer patients with operable T1,2, estrogen receptor‑positive, node‑negative cancer who were assessed using the Oncotype DX gene profile, as well as patients with locally advanced disease prior to and following neoadjuvant systemic treatment. GRP78 values were compared between the 2 groups, and prior to and following systemic treatment. Association analyses between GRP78 expression and prognostic markers were also performed. Cox regression analysis was used to examine the impact of these variables on disease‑free survival (DFS). No differences in cytoplasmic GRP78 expression were observed. By contrast, the rates of cell surface GRP78 expression were 74.1% in the early stage operable patients, 36% in neoadjuvant systemic treatment patients prior to treatment and 62.5% in patients following systemic treatment (P<0.039). Positive cell surface GRP78 expression was associated with increased expression of the progesterone receptor (P=0.024), p53 expression (P=0.022) and improved DFS (P=0.047). In the case of GRP78 positivity, a trend for a superior response to chemotherapy was observed (P=0.19). The results of the present study indicated that cell surface GRP78 may be used as a marker for good prognosis in breast cancer and a potential marker for response to chemotherapy.

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