Expression of NF-kappaB and human telomerase reverse transcriptase in gastric cancer and precancerous lesions.

Abstract

To investigate the expression of NF-kappaBp65 protein and human telomerase reverse transcriptase (hTERT) and their correlation in gastric cancer and precancerous lesions. Forty-one patients with primary gastric cancer, 15 with dysplasia, 23 intestinal metaplasia and 10 with normal gastric mucosa were included in this study. Expression of NF-kappaBp65 protein, hTERT mRNA and protein were determined by immunohistochemistry and in situ hybridization. The rate of p65 expression in normal gastric mucosa, intestinal metaplasia, dysplasia and carcinoma was 0%, 34.78%, 53.33% and 60.98%, respectively, while the rate of hTERT mRNA expression was 10.00%, 39.13%, 66.67% and 85.37% and the rate of hTERT protein expression was 0%, 30.43%, 60.00% and 78.05%, respectively. All the three parameters were significantly increased in dysplasia and carcinoma compared to normal mucosa, while the expression levels were also significantly higher in carcinoma than in intestinal metaplasia (P<0.05). In gastric cancer tissues, nuclear staining rates of p65 and hTERT protein were both significantly associated with the degree of differentiation, lymph node metastasis, clinical stage and invasion depth (P<0.05). However, hTERT mRNA expression was only significantly associated with clinical stage. There was a positive correlation between p65 and hTERT mRNA (rs=0.661-0.752, P<0.01), and between hTERT protein and hTERT mRNA (rs=0.609-0.750, P<0.01). NF-kappaBp65 and hTERT expressions are upregulated at the early stage of gastric carcinogenesis. NF-kappaB activation may contribute to hTERT expression and thereby enhance telomerase activity, which represents an important step in carcinogenesis progress.