title: Pretherapy nuclear factor-kappaB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma.
abstract: BACKGROUND
  Transcriptional factor nuclear factor-kappaB (NF-kappaB) seems to be associated with aggressive clinical biology (chemoradiation resistance and metastatic progression) of esophageal cancer. We hypothesized that activated NF-kappaB would define clinical biology irrespective of the type of chemotherapy or sequence administered.
  
  
  METHODS
  Pretherapy and/or posttherapy cancer specimens were examined for activated NF-kappaB and correlated with pathologic response to chemoradiation, metastatic potential, overall survival, disease-free survival, and type of chemotherapy or sequence used.
  
  
  RESULTS
  Eighty patients undergoing chemotherapy and concurrent radiation were studied. Activated NF-kappaB prior to any therapy was associated with the lack of complete pathologic response (pathCR, P = 0.006). Forty-five (78%) of 58 patients achieving <pathCR had activated NF-kappaB in pretherapy and/or posttherapy cancer specimens versus 2 (9%) of 22 patients with pathCR (P = 0.001). Twenty-four (51%) of 47 patients with activated NF-kappaB in cancer developed metastases versus 7 (21%) of 22 patients with negative NF-kappaB in cancer (P = 0.01). At a median follow-up of 32 months, 25 (53%) of 47 patients with activated NF-kappaB cancer had died versus 3 (9%) of 33 patients with negative NF-kappaB cancer. NF-kappaB activation was the only independent predictor of disease-free survival (P = 0.01) and overall survival (P = 0.007) in a multivariate model. The class of chemotherapy or its sequence had no effect on NF-kappaB expression or patient outcome.
  
  
  CONCLUSIONS
  Our data are the first to show that pretreatment-activated NF-kappaB significantly correlates with clinical biology of esophageal cancer, and most importantly, with pathCR. To therapeutically exploit NF-kappaB-regulated genes and their pathways, further research is warranted.
authors.affiliation: Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA. jajani@mdanderson.org
authors.forename: Julie G
authors.initials: JG
authors.lastname: Izzo
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Correa
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.forename: Usha
authors.initials: U
authors.lastname: Malhotra
authors.forename: Clifford K S
authors.initials: CK
authors.lastname: Chao
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Joe
authors.initials: J
authors.lastname: Ensor
authors.forename: Alexander
authors.initials: A
authors.lastname: Dekovich
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Walter N
authors.initials: WN
authors.lastname: Hittelman
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B