P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma
Por:
Vega G.G., Avilés-Salas A., Chalapud J.R., Martinez-Paniagua M., Pelayo R., Mayani H., Hernandez-Pando R., Martinez-Maza O., Huerta-Yepez S., Bonavida B., Vega M.I.
Publicada:
16 oct 2015
Resumen:
Background: The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients. Methods: Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-?B expressions were determined. Kaplan Meier analysis was assessed. Results: Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38- and 34 % for p38+ and for OS was 83 % for p38- and 47 % for p38+. The p-p38+ tissues expressed Bcl-2 and 90 % of p-p38- where Bcl-2-. The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-?B. Conclusion: The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors. © 2015 Vega et al.
Filiaciones:
Vega G.G.:
Univ Nacl Autonoma Mexico, Fac Med, Programa Posgrad, Doctorado Ciencias Biomed, Mexico City, DF, Mexico
Avilés-Salas A.:
Instituto Nacional de Cancerología, SSA, Departamento de Patología, México City, Mexico
Chalapud J.R.:
Servicio de Hematología, Instituto Nacional de Cancerología, SSA, México City, Mexico
Martinez-Paniagua M.:
Unidad de Investigación Médica en Inmunología e Infectología, CMN La Raza, IMSS, México City, Mexico
Pelayo R.:
Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico
Mayani H.:
Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico
Hernandez-Pando R.:
Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, SSA, Departamento de Patología Experimental, México City, Mexico
Martinez-Maza O.:
Immunology and Molecular Genetics, David Geffen School of Medicine UCLA, Department of Microbiology, Los Angeles, CA, United States
Huerta-Yepez S.:
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, SSA, México City, Mexico
Bonavida B.:
Immunology and Molecular Genetics, David Geffen School of Medicine UCLA, Department of Microbiology, Los Angeles, CA, United States
Vega M.I.:
Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico
Immunology and Molecular Genetics, David Geffen School of Medicine UCLA, Department of Microbiology, Los Angeles, CA, United States
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