title: Association of activated transcription factor nuclear factor kappab with chemoradiation resistance and poor outcome in esophageal carcinoma.
abstract: OBJECTIVE
  The lack of effective treatment for localized esosphageal cancer leads to poor patient outcome. Nuclear factor kappaB (NF-kappaB), a transcriptional factor, is constitutively activated or treatment induced in esophageal cancer and may influence treatment outcomes.
  
  
  METHODS
  Pre- and post-treatment cancer specimens from patients enrolled onto a clinical trial were studied for the expression of activated NF-kappaB protein and it was correlated with histologic features, pathologic response, metastatic potential, overall survival (OS), and disease-free survival (DFS).
  
  
  RESULTS
  Forty-three patients undergoing the same therapy on a protocol were studied. Twenty-one (72%) of 29 patients achieving less than complete pathologic response (pathCR) had NF-kappaB positive cancer, but only one (7%) of 14 patients achieving pathCR had NF-kappaB positive cancer (P = < .001). Activated NF-kappaB was significantly associated with aggressive pathologic features such as perineural, lymphatic, and/or vascular invasion (P = .0004). Eight (38%) of 21 NF-kappaB positive patients developed metastases compared to none of 22 NF-kappaB negative patients (P = .001). At a median follow-up of 23 months, 10 (48%) of 21 NF-kappaB positive patients had died compared to only one (5%) of 22 NF-kappaB negative patients (P = .0013). Observations were similar for DFS (P = .0006). In a multivariate model (using baseline stage, pathCR or less than pathCR, age, presence of metastatic lymph nodes in the surgical specimen, and NF-kappaB expression) NF-kappaB activation was the only independent predictor of DFS (P = .010) and OS (P = .015).
  
  
  CONCLUSIONS
  Our data suggest that esophageal cancers with activated NF-kappaB have aggressive clinical biology and poor treatment outcome. Additional understanding of NF-kappaB regulated pathways may uncover potential therapeutic targets.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Izzo
authors.forename: Usha
authors.initials: U
authors.lastname: Malhotra
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.forename: Joe
authors.initials: J
authors.lastname: Ensor
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lee
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: K S Clifford
authors.initials: KS
authors.lastname: Chao
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; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D016328:NF-kappa B; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin