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Clinical Biology of Esophageal Adenocarcinoma after Surgery Is Influenced by Nuclear Factor-B Expression

Departments of ¹ Experimental Therapeutics, ² Pathology, ³ Cardiovascular and Thoracic Surgery, ⁴ Radiation Oncology, ⁵ Molecular and Cellular Oncology; and ⁶ Gastrointestinal Medical Oncology, The University of M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Jaffer A. Ajani, Department of Gastrointestinal Medical Oncology, Unit # 426, The Univerisity of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-2828; Fax: 1-713-745-1163. E-mail: jajani{at}mdanderson.org

Background: The expression of transcriptional factor nuclear factor B (NF-B) in untreated esophageal cancer specimens from patients who receive preoperative chemoradiation is associated with aggressive clinical biology. We hypothesized that nuclear NF-B 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-B 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-B 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-B 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-B 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-B status significantly correlates with DFS and OS for patients with esophageal adenocarcinoma undergoing surgery as primary therapy. NF-B 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. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1200–5)