Correlation of the protein expression of GRP78 and BIK/NBK with prognostic markers in patients with breast cancer and neoadjuvant chemotherapy.

The objective of this study was to determine the frequency of expression of GRP78 and BIK/NBK proteins, as well as to evaluate their correlation with prognostic factors for clinical use in patients with locally advanced breast cancer (LABC) or preoperative chemotherapy (PC). An observational, analytical and retrospective study that evaluated the expression of BIK/NBK and GRP78 by means of immunohistochemistry in paraffin-embedded tumour tissue samples obtained before the start of PC was executed. GRP78 was positive in 93.3% and BIK/NBK was positive in 40% of the samples analysed. Correlation of GRP78 expression with Ki67 expression (Rho = 0.732,  = .039), and of BIK/NBK expression with Ki67 expression (Rho = 0.777,  = .023) and number of residual lymph nodes (Rho = 0.619,  = .014) was observed. Given the correlation observed, association studies of the expression of GRP78 and BIK/NBK with clinical and pathological response, recurrence and survival should be carried out in a greater number of patients with LABC or PC.Impact Statement There are reports of the overexpression of GRP78 in various types of cancer cell lines and tumour biopsies, including breast cancer, with participation in resistance to adjuvant chemotherapeutic agents (topoisomerase inhibitors including Adriamycin). On the other hand, BIK/NBK has been observed expressed associated with poor outcomes in breast cancer. There are no studies of the expression of both biomarkers in patients with preoperative chemotherapy, including locally advanced breast cancer (LABC) or their correlation with prognosis markers of clinical use. We observed a correlation of higher expression percentage of GRP78 and BIK/NBK with higher expression of Ki67, a marker of poor prognosis in breast cancer, in addition to a significant correlation of higher percentage of BIK/NBK expression with a greater number of residual nodes in patients with LABC or PC. There is a potential prognostic value of GRP78 and BIK/NBK in the pathological response that merits further study addressing their interaction with other proteins, their cellular location in relation to the clinical stages of breast cancer, and their association with prognosis (clinical and pathological response, recurrence, disease free period and survival) in a greater number of patients with LABC or PC.