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Nuclear Factor-B p65 (RelA) Transcription Factor Is Constitutively Activated in Human Gastric Carcinoma Tissue

Departments of Cancer Therapy and Research [N. S., T. M., K. H., M. K.], Anatomic Pathology [T. Yao, M. Ts.], Surgery and Oncology [H. N., K. N., A. U., M. Ta.], and Medical Informatics [T. Yam.], Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

Purpose: Activation of transcription factor nuclear factor-B (NF-B) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-B is constitutively activated in human gastric carcinoma tissues and, if so, to determine any correlation between NF-B activity and clinicopathological features of gastric carcinoma.

Experimental Design: NF-B activation was determined by immunohistochemical analysis of formalin-fixed, paraffin-embedded specimens from 64 gastric carcinoma patients. We quantified nuclear staining of RelA as a marker of NF-B activation.

Results: Nuclear translocation of RelA was significantly high in tumor cells in comparison to that in adjacent normal epithelial cells (22.5 ± 2.4% versus 8.6 ± 1.5%, P < 0.0001). There was a significant correlation between NF-B activation (nuclear translocation of RelA) and expression of urokinase-type plasminogen activator, an invasion-related factor and target of NF-B in tumor cells ( = 0.393; P = 0.0013). NF-B activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion of tumor cells (P = 0.0126), depth of invasion (P = 0.0539), peritoneal metastases (P = 0.0538), and tumor size (P = 0.0164).

Conclusions: Collectively, the data show that NF-B is constitutively activated in human gastric carcinoma tissues and suggest that NF-B activity is related to tumor progression due to its transcriptional regulation of invasion-related factors such as urokinase-type plasminogen activator.

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