title: P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma.
abstract: 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-κB 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-κB.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico. gabriel.g.vega@gmail.com.|Facultad de Medicina Programa de Posgrado, Doctorado en Ciencias Biomédicas UNAM, México City, DF, Mexico. gabriel.g.vega@gmail.com.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Vega
authors.affiliation: Departamento de Patología, Instituto Nacional de Cancerología, SSA, México City, México. aaviles@incan.edu.mx.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Avilés-Salas
authors.affiliation: Servicio de Hematología, Instituto Nacional de Cancerología, SSA, México City, México. injuan@hotmail.com.
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Chalapud
authors.affiliation: Unidad de Investigación Médica en Inmunología e Infectología, CMN La Raza, IMSS, México City, México. mapamean@yahoo.com.mx.
authors.forename: Melisa
authors.initials: M
authors.lastname: Martinez-Paniagua
authors.affiliation: Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico. rosanapelayo@gmail.com.
authors.forename: Rosana
authors.initials: R
authors.lastname: Pelayo
authors.affiliation: Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico. hmayaniv@prodigy.net.mx.
authors.forename: Héctor
authors.initials: H
authors.lastname: Mayani
authors.affiliation: Departamento de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran, SSA, México City, México. rhdezpando@hotmail.com.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernandez-Pando
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine UCLA, Los Angeles, CA, USA. omartinez@mednet.ucla.edu.
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martinez-Maza
authors.affiliation: Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, SSA, México City, México. shuertay@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Huerta-Yepez
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine UCLA, Los Angeles, CA, USA. bbonavida@mednet.ucla.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonavida
authors.affiliation: Oncology Research Unit, Oncology Hospital, Siglo XXI National Medical Center, IMSS, Mexico City, Mexico. marioi@unam.mx.|Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine UCLA, Los Angeles, CA, USA. marioi@unam.mx.
authors.forename: Mario I
authors.initials: MI
authors.lastname: Vega
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis; D014750:Vincristine / Q000008:administration & dosage; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D048051:p38 Mitogen-Activated Protein Kinases; D011241:Prednisone