BAG-1/SODD, HSP70, and HSP90 are potential prognostic markers of poor survival in node-negative breast carcinoma

SummaryThe objective of this study was to analyze the expression and clinical role of 13 signaling molecules in a large cohort of breast carcinoma patients with long follow-up period. Breast carcinomas (n = 410) were analyzed for protein expression of phosphorylated mitogen-activated protein kinases (p-ERK, p-JNK, p-p38) and phosphoinositide 3-kinase signaling pathway proteins (p-AKT, p-mTOR, p-p70S6K); the BAG family proteins BAG-1 and BAG-4/SODD; the antiapoptotic protein Bcl-2; the inhibitor of apoptosis family member Survivin; and the heat shock protein family members HSP27, HSP70, and HSP90. Protein expression was studied for association with clinicopathological parameters and survival. Significantly higher expression of p-AKT (P < .001), p-mTOR (P < .001), p-p70S6K (P < .001), Bcl-2 (P < .001), BAG-4/SODD (P < .001), HSP27 (P < .001), HSP70 (P = .012), HSP90 (P < .001), and Survivin (P = .004) was found in infiltrating ductal and lobular carcinomas compared to mucinous carcinomas. Bcl-2 expression was significantly higher in grades 1 and 2 compared to grade 3 carcinomas (P < .001). p-AKT expression was higher in tumors more than 2 cm (P = .027), whereas p-mTOR expression was lowest in tumors more than 5 cm (P = .019). Higher BAG-4/SODD, HSP70, and HSP90 expression was associated with poor overall survival (P = .016, P = .039, and P = .023, respectively) in univariate analysis, whereas the only independent prognosticator in Cox multivariate survival analysis was tumor diameter (P = .003). In conclusion, BAG-4/SODD, HSP70, and HSP90 are potential prognostic markers in node-negative breast carcinoma that merit further research.