Activated nuclear factor-kappa B and cytokine profiles in the esophagus parallel tumor regression following neoadjuvant chemoradiotherapy

Dis Esophagus. 2005;18(4):246-52. doi: 10.1111/j.1442-2050.2005.00497.x.


Esophageal adenocarcinoma is increasing in incidence; it relates to chronic gastroesophageal reflux, it is difficult to cure, and treatment modalities increasingly use chemotherapy and radiation therapy prior to resectional surgery. Nuclear factor-kappa B (NF-kappaB) is a pleiotropic transcription factor that regulates several genes for cytokines and enzymes involved in inflammation and immunity, and we have previously described sequential expression of NF-kappaB from the normal esophagus through Barrett's metaplasia to adenocarcinoma. The aim of this exploratory study was to assess the NF-kappaB status and cytokine profiles pre- and post-chemoradiotherapy for esophageal adenocarcinoma. Fresh biopsy specimens obtained from 20 patients with esophageal adenocarcinoma and normal adjacent squamous epithelium were obtained pre-, during and post-chemoradiotherapy, and NF-kappaB expression was analyzed by electrophoretic mobility shift assay. The cytokine protein content of interleukin-1 beta (IL-1beta) and interleukin-8 (IL-8) of tissue homogenates was measured using the ELISA technique. NF-kappaB was constitutively activated in tumor tissues from esophageal adenocarcinoma but was not detected in adjacent normal esophageal mucosa. Elevated levels of IL-1beta and IL-8 were significantly (P < 0.05) higher in tumor tissues compared to control tissues. Patients with a major or complete pathological response (responders) were associated with absence of activated NF-kappaB from nuclear extracts after treatment. Moreover, IL-1beta and IL-8 levels were significantly (P < 0.05) down-regulated in tumor tissues from patients who demonstrated a complete pathological response. No differences in NF-kappaB, IL-1beta and IL-8 levels were detected pre- and post-treatment in patients who did not have a major or complete pathological response (non-responders). The study suggests that monitoring of molecular and cytokine patterns in patients undergoing this neoadjuvant regimen may help subselect the cohort that derives most benefit from the multimodal approach.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols
  • Biopsy
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Down-Regulation
  • Epithelium / pathology
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Esophagectomy
  • Esophagus / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Interleukin-1 / analysis*
  • Interleukin-8 / analysis*
  • Male
  • NF-kappa B / analysis*
  • Neoadjuvant Therapy*
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant
  • Remission Induction


  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Interleukin-1
  • Interleukin-8
  • NF-kappa B
  • Cisplatin
  • Fluorouracil