BIK and GRP78 protein expression as possible markers of response to preoperative chemotherapy and survival in breast cancer

Abstract

Objective: BIK and GRP78 have shown differential expression profiles in breast cancer (BC) tissue, in addition to its important participation in the pathophysiology of cancer. The purpose of this study was to evaluate the association of BIK and GRP78 protein expression with clinical and pathologic response to preoperative chemotherapy, recurrence, disease-free survival (DFS) and overall survival (OS), in patients with BC.

Material and methods: Fifty-three patients who received preoperative chemotherapy where included in an observational, analytical and retrospective study to assess the BIK and GRP78 protein expression by immunohistochemistry in microarrays of BC tissue obtained before treatment. Associations between BIK and GRP78 expression with clinicopathological characteristics, clinical and pathologic response to preoperative chemotherapy, and recurrence were analyzed using Chi-square or Fishers exact test. OS and postoperative DFS were assessed at 5-year follow-up by Kaplan-Meir curves, and the difference according to BIK and GRP78 expression was evaluated using the log-rank test. Bivariate analysis was performed using Cox risk proportion model. A p value 0.05 was considered to be statistically significant.

Results: BIK and GRP78 staining revealed positive expression in 37 (71.2) and 35 patients (72.9) respectively. Association between pathological complete response (pCR) and positive expression of BIK (p 0.046), as well as between clinical complete response (cCR) and negative expression of GRP78 was observed (p 0.048). Patients with expression of GRP78 had lower DFS (HR 3.46; 95 CI 1.01-11.80; p 0.047) and shorter OS (HR 3.49; 95 CI 1.04 a 11.72; p 0.043).

Conclusion: When finding association of GRP78 and BIK protein expression with the response (clinical and pathologic respectively) to preoperative chemotherapy, and GRP78 with DFS and OS, in patients with BC, our results suggest a potential prognostic value of both proteins; however, a larger sample size is required to confirm this.