title: BAG-1/SODD, HSP70, and HSP90 are potential prognostic markers of poor survival in node-negative breast carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norways. Electronic address: bend@medisin.uio.no.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: National Advisory Unit on Late Effects after Cancer Treatment, Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Valborg Reinertsen
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Don
authors.initials: D
authors.lastname: Trinh
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Wenche
authors.initials: W
authors.lastname: Reed
authors.affiliation: Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
authors.forename: Per Johannes
authors.initials: PJ
authors.lastname: Bøhler
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018275:Carcinoma, Lobular / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis*; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D046888:Tissue Array Analysis / Q000379:methods; D014157:Transcription Factors / Q000032:analysis*; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: C091732:BCL2-associated athanogene 1 protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D014157:Transcription Factors
keywords: Apoptosis; Breast carcinoma; Immunohistochemistry; Intracellular signaling; Proliferation; Survival