title: Therapy-induced expression of NF-kappaB portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation.
abstract: Activated nuclear factor-kappa B (NF-kappaB) in the pretreatment cancer tissue of patients with localized esophageal adenocarcinoma (LEA) undergoing preoperative chemoradiation is associated with poor prognosis. It is known that constitutively activated NF-kappaB prior to any therapy portends poor prognosis, and it is also known that activated NF-kappaB in the treated specimen is associated with poor prognosis. However, the prognosis of patients who have treatment-induced activation of NF-kappaB (meaning their cancers activate NF-kappaB during or after therapy) is not been reported. We hypothesized that the treatment-induced activation of NF-kappaB would impart poor prognosis similar to that imparted by constitutively activated NF-kappaB cancer. Patients with LEA who had undergone preoperative chemoradiation plus surgery and had pre- and post-therapy cancer tissue available were selected. Pre- and post-therapy cancer tissues were stained by immunohistochemistry for nuclear staining of NF-kappaB. The overall survival (OS) and disease-free survival were assessed and compared for patients who had intrinsic constitutively activated NF-kappaB cancer with those who had induced activation of NF-kappaB only post-therapy. A total of 41 patients with LEA were investigated. Twenty-five patients had NF-kappaB positive cancer at baseline, and 16 had NF-kappaB negative cancer at baseline but became positive post-therapy. There was no difference in the location, histology grade, clinical stage, or the curative resection (RO) resection rate in the two populations. OS (P = 0.71), disease-free survival (P = 0.86), and median survivals (Converters: 24 months [95% confidence intervals: 7.78 to 40.22]vs. Nonconverters: 34.13 months [95% confidence intervals: 3.54 to 64.27]) were not different between the two groups. Our data suggest that activation of NF-kappaB in response to stress/injury of therapy leads to poor OS. These results need to be confirmed in a larger number of patients. It may be that only pre-therapy evaluation of NF-kappaB is insufficient to assess prognosis of patients with LEA. Additional implications include that when effective anti-NF-kappaB therapies become available, they may have to be considered in patients whose cancers do not have constitutively activated NF-kappaB or cancer may have to be monitored during therapy with biomarker assessments.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Izzo
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: T-T
authors.initials: TT
authors.lastname: Wu
authors.forename: P
authors.initials: P
authors.lastname: Huang
authors.forename: J-S
authors.initials: JS
authors.lastname: Lee
authors.forename: Z
authors.initials: Z
authors.lastname: Liao
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: M S
authors.initials: MS
authors.lastname: Bhutani
authors.forename: W
authors.initials: W
authors.lastname: Hofstetter
authors.forename: D
authors.initials: D
authors.lastname: Maru
authors.forename: M-C
authors.initials: MC
authors.lastname: Hung
authors.forename: J A
authors.initials: JA
authors.lastname: Ajani
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000601:surgery / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011379:Prognosis
chemical_list: D016328:NF-kappa B