Clinical biology of esophageal adenocarcinoma after surgery is influenced by nuclear factor-kappaB expression.
BACKGROUND
The expression of transcriptional factor nuclear factor kappaB (NF-kappaB) in untreated esophageal cancer specimens from patients who receive preoperative chemoradiation is associated with aggressive clinical biology. We hypothesized that nuclear NF-kappaB would define clinical biology even when surgery is used as primary therapy.


METHODS
Consecutive patients who did not receive any preoperative therapy were selected. Surgical cancer specimens were examined for nuclear NF-kappaB and correlated with overall survival (OS) and disease-free survival (DFS).


RESULTS
One hundred twenty-three patients (stage I, 9%; stage II, 24%; stage III, 53%; stage IV, 15%) with adenocarcinoma who underwent surgery as primary therapy were analyzed. Most patients were men (90%) and the median age was 63 years. For all 123 patients, the median DFS was 21 months and the median OS was 28 months. Nuclear NF-kappaB was associated with shortened DFS (P = 0.001) in 123 patients but also in stage II (P = 0.03) and stage III (P = 0.04). Nuclear NF-kappaB was associated with shortened OS (P = 0.002) in 123 patients and in stage II (P = 0.04) and showed trend in stage III (P = 0.17). Numbers are too small for stages I and IV. In multivariate models, nuclear NF-kappaB was an independent predictor for both DFS and OS (P = 0.005 and P = 0.01).


CONCLUSIONS
Our data are the first to show that NF-kappaB status significantly correlates with DFS and OS for patients with esophageal adenocarcinoma undergoing surgery as primary therapy. NF-kappaB is an independent prognosticator of outcome, even for individual stages (e.g., stages II and III). More comprehensive molecular studies could help the design of strategies to individualize therapy of esophageal adenocarcinoma.
Izzo
Julie G
JG
Department of Experimental Therapeutics, The Univerisity of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Malhotra
Usha
U
Wu
Tsung-Teh
TT
Luthra
Rajalakshmi
R
Correa
Arlene M
AM
Swisher
Stephen G
SG
Hofstetter
Wayne
W
Chao
K S Clifford
KS
Hung
Mien-Chie
MC
Ajani
Jaffer A
JA
D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis*; D011379:Prognosis
D014408:Biomarkers, Tumor; D016328:NF-kappa B