Increased expression of RelA/nuclear factor-κB protein correlates with colorectal tumorigenesis

Objective: To identify the role of ReIA/nuclear factor-kappaB, an important inhibitor of apoptosis in colorectal tumorigenesis, we examined the expression of ReIA in normal colorectal mucosa (n = 10), colorectal adenomas (n = 30) and colorectal adenocarcinomas (n = 30). Furthermore, the association of RelA expression with tumor cell apoptosis, proliferation, and expression of Bcl-2/Bcl-X-L was also studied. Methods: Paraffin sections were stained with monoclonal antibodies directed against RelA, Bcl-2, Bcl-X-L, and Ki-67 to assess protein expression patterns in normal, adenomatous and colon cancer tissue. Apoptotic cells were detected by terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) using an in situ detection kit. Results: The results of immunohistochemical staining revealed that expression of RelA, Bcl-2, BCI-X-L, and Ki-67 labeling index (LI) significantly increased in the transition from adenoma with low dysplasia to adenocarcinoma. This transition was associated with a significant decrease in the apoptotic index (AI) and a significant increase in the Ki-67 LI. The expression of RelA correlated inversely with the AI and correlated positively with the expression of Bcl-2, Bcl-X-L, and Ki-67 LI in the transition from low-grade dysplasia to adenocarcinoma. Conclusion: Our results suggest that increased expression of ReIA/nuclear factor-kappaB plays an important role in the transition from colorectal adenoma with low-grade dysplasia to adenocarcinoma in the pathogenesis of colon cancer in humans. Copyright (C) 2003 S. Karger AG, Basel.