Association of activated transcription factor nuclear factor κB with chemoradiation resistance and poor outcome in esophageal carcinoma

Purpose The lack of effective treatment for localized esosphageal cancer leads to poor patient outcome. Nuclear factor kappa B (NF-kappa B), a transcriptional factor, is constitutively activated or treatment induced in esophageal cancer and may influence treatment outcomes. Patients and Methods Pre- and post-treatment cancer specimens from patients enrolled onto a clinical trial were studied for the expression of activated NF-kappa B protein and it was correlated with histologic features, pathologic response, metastatic potential, overall survival (OS), and disease-free survival (DFS). Results Forty-three patients undergoing the same therapy on a protocol were studied. Twenty-one (72%) of 29 patients achieving less than complete pathologic response (pathCB) had NF-kappa B positive cancer, but only one (7%) of 14 patients achieving pathCB had NF-kappa B positive cancer (P = <.001). Activated NF-kappa B was significantly associated with aggressive pathologic features such as perineural, lymphatic, and/or vascular invasion (P =.0004). Eight (38%) of 21 NF-kappa B positive patients developed metastases compared to none of 22 NF-kappa B negative patients (P =.001). At a median follow-up of 23 months, 10 (48%) of 21 NF-kappa B positive patients had died compared to only one (5%) of 22 NF-kappa B negative patients (P =.0013). Observations were similar for DFS (P =.0006). In a multivariate model (using baseline stage, pathCR or less than pathCR, age, presence of metastatic lymph nodes in the surgical specimen, and NF-kappa B expression) NF-kappa B activation was the only independent predictor of DFS (P =.010) and OS (P =.015). Conclusion Our data suggest that esophageal cancers with activated NF-kappa B have aggressive clinical biology and poor treatment outcome. Additional understanding of NF-kappa B regulated pathways may uncover potential therapeutic targets.