Background: The expression of transcriptional factor nuclear factor κB (NF-κB) in untreated esophageal cancer specimens from patients who receive preoperative chemoradiation is associated with aggressive clinical biology. We hypothesized that nuclear NF-κB 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-κB 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-κB 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-κB 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-κB 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-κB status significantly correlates with DFS and OS for patients with esophageal adenocarcinoma undergoing surgery as primary therapy. NF-κB 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.
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