Association of Constitutive Nuclear Factor-κB Activation With Aggressive Aspects and Poor Prognosis in Cervical Cancer

Introduction: Although nuclear factor-kappa B (NF-kappa B) is generally believed to be involved in carcinogenesis, the relationship between NF-kappa B activation and progression of cervical cancer in clinical settings has not been reported. In this study, we investigated the association of NF-kappa B activation with aggressive aspects and prognosis in cervical cancer. Methods: Nuclear factor-kappa B Subunits p65 and p50 were detected in 159 paraffin tissues including normal cervical, precancerous (squamous intraepithelial lesions), and cervical carcinoma tissues by immunohistochemistry. Nuclear factor-kappa B nuclear translocation and DNA-binding activity in precancerous or carcinoma tissues were examined by Western blot and electrophoretic mobility shift assay, respectively. Results: A gradual NF-kappa B activation from normal cervical epithelial cells to precancerous and carcinoma cells was detected by immunohistochemistry (nuclear expression of p65 and p50, P < 0.001), Western blot (NF-kappa B nuclear translocation), and electrophoretic mobility shift assay (enhanced DNA-binding activity). In 79 cancer tissues, increased nuclear p65, an active NF-kappa B form, was correlated with poor tumor grade, lymphatic metastasis, interstitial invasion, and larger tumor size (P < 0.05). Similarly, increased nuclear p50 was correlated with poor tumor grade, interstitial invasion, and larger tumor size (P < 0.05). Moreover, increased nuclear p65 was associated with lower survival rate in patients with cancer (P < 0.05). Conclusions: Constitutive NF-kappa B activation is correlated to tumor progression, aggressive behaviors, and poor prognosis in cervical cancer, suggesting that NF-kappa B is a tumor promoter, a prognostic indicator, and a possible therapeutic target for this malignant disease.