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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Aged, Aged, 80 and over, Biomarkers, Breast Neoplasms, Carcinoma, Cell Nucleus, Cohort Studies, Disease Progression, Enzyme Activation, Female, Humans, JNK Mitogen-Activated Protein Kinases, Middle Aged, Pleural Effusion, Receptor, ErbB-2, p38 Mitogen-Activated Protein Kinases.
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Are the mitogen-activated protein kinases ( MAPK ) p38 and JNK markers of tumor progression in breast carcinoma? Context: To investigate the activation of mitogen-activated protein kinases (MAPK) in breast carcinoma effusions and to analyze its relationship to anatomic site and clinical parameters. Activated MAPK (p-ERK, p-JNK, and p-p38) expression was studied in 42 effusions and 51 corresponding solid tumors (23 primary, 28 metastases) using immunohistochemistry (IHC). Hormone receptor and HER2 status, proliferation (Ki-67), and apoptosis (p85-PARP fragment) were assessed. MAPK levels, activity, and activation ratio (phospho/pan-MAPK ratio) were analyzed in 19 effusions using immunoblotting (IB). Nuclear expression of p-p38 and p-JNK was significantly higher in effusions compared with both primary tumors (P < 0.001 for p-JNK, P = 0.011 for p-p38) and lymph node metastases (P = 0.003 for p-JNK, P = 0.025 for p-p38) but was not accompanied by apoptosis. IB showed pan-ERK and p-ERK in 18/19 effusions, pan-JNK and p-JNK in 18/19 and 17/19 effusions, respectively, and pan-p38 and p-p38 in 19/19 and 17/19 specimens, respectively. In univariate survival analysis of all cases, advanced disease stage (P = 0.041), previous chemotherapy (P = 0.004), and radiation (P = 0.001) and higher Ki-67 scores (P = 0.01) correlated with worse overall survival (OS). In Cox multivariate analysis, stage (P = 0.018), chemotherapy (P = 0.024), radiation (P = 0.017), and ER status (P = 0.002) were independent prognosticators of OS. Quantitative analysis of IB data showed that higher p38 activation ratio correlates with shorter OS (P = 0.01).
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This study presents first evidence of in vivo activation of MAPK in breast carcinoma effusions. The elevated JNK and p38 activation in effusions may be a stress-related mechanism providing breast carcinoma cells with survival advantages rather than a drive towards apoptosis. p38 and Ki-67 may be new prognostic markers for patients with breast cancer effusions. Final Decision: yes