[Immunohistochemical analysis of nuclear factor, p38, and cyclin D1 proteins in premalignant lesions and carcinomas of the colorectal mucosa].

Background/aims: Nuclear factor-kappaB p65 (NF-kappaB p65), nuclear factor-kappaB1 p50 (NF-kappaB p50) have been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. Recently, p38 mitogen-activated protein kinase (MAPK)/ NF-kappaB/ cyclin D1 signaling pathway has been shown to play an important part in the pathogenesis of human cancers. This study was designed to investigate the expression of NF-kappaB p65, NF-kappaB p50, p38 MAPKalpha, and cyclin D1 proteins in premalignant lesions of colon and colorectal adenocarcinoma.

Methods: Paraffin sections of 20 normal mucosa, 20 low-grade tubular adenoma, 20 high-grade tubular adenoma and 64 adenocarcinoma tissues were analysed immunohistochemically for the expression of NF-kappaB p65, NF-kappaB p50, p38 MAPKalpha, and cyclin D1 proteins.

Results: The expression of NF-kappaB p65, NF-kappaB p50, and p38 MAPKalpha proteins were significantly higher in adenocarcinoma tissue in comparison with that in normal mucosa, low-grade tubular adenoma, and high-grade tubular adenoma tissues. Expression of NF-kappaB p50 was more frequent in poorly differentiated histologic grade, presence of nodal metastasis, and advanced stage. Expression of p38 MAPKalpha protein was higher in advanced tumor stage, presence of nodal metastasis and advanced stage. Synchronous expression of NF-kappaB p65, NF-kappaB p50, p38 MAPKalpha, and cyclin D1 proteins were significantly higher in adenocarcinoma tissue.

Conclusions: With the increased expression of NF-kappaB p65, NF-kappaB p50, and p38 MAPKalpha proteins, p38 MAPK/ NF-kappaB/ cyclin D1 signaling pathway may play a role in the pathogenesis of colorectal carcinoma.