The 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 2cm (P=.027), whereas p-mTOR expression was lowest in tumors more than 5cm (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.
Keywords: Apoptosis; Breast carcinoma; Immunohistochemistry; Intracellular signaling; Proliferation; Survival.
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