Background: Some reports have confirmed that occurrence and development of tumor are related with lots of oncogene, anti-oncogene and cytokine. This study was to detect the expression of TNFmRNA, tumor necrosis factor (TNF) and TNF receptor (TNFR) in the gallbladder mucosa which developed from hyperplasia, dysplasia to carcinoma, and to further discuss the pathogenecity of gallbladder carcinoma.
Methods: The expression of TNFmRNA, TNF and TNFR was detected by in situ hybridization and immunohistochemistry on the surgical specimens of hyperplasia, dysplasia and carcinoma of the gallbladder.
Results: The percentage of positive cells expressed TNFmRNA in the gallbladder mucosa was 0%, 20%, and 90%, respectively in hyperplasia, dysplasia and carcinoma (P<0.05). The percentage of positive mononuclear cells (MNCs) expressed TNFmRNA in hyperplasia, dysplasia and carcinoma of gallbladder tissues was 15%, 85%, and 90%, respectively (P<0.05). The number of positive MNC high-power field (Hpf) was 4.85+/-1.50, 6.00+/-2.71, and 9.33+/-3.07, respectively (P<0.05). The number of carcinoma cells and MNCs expressed by TNFmRNA per high-power field was increased with the increase of tumor stage. The number of carcinoma cells/Hpf in stages I-III and IV-V was 9.13+/-4.39 and 7.13+/-2.53 (P<0.05), and that of MNC/Hpf was 14.80+/-4.02 and 11.10+/-2.23 (P<0.01). The number of carcinoma cells and MNCs expressed by TNFmRNA per Hpf was increased with the increase of tumor size. In tumors of more than 2 cm or less than 2 cm in diameter, the number of positive carcinoma cells/Hpf was 14.00+/-4.20 and 8.83+/-4.96, respectively (P<0.05), but that of MNC/Hpf was 10.50+/-2.54 and 7.00+/-2.83 (P<0.05). The pattern of TNF protein expression was similar to that of TNFmRNA, whereas TNF protein expression was more frequent and extensive than TNFmRNA expression. TNFR was expressed in endothelial cells and MNCs of carcinoma, and was negative in mucosal epithelial cells and tumor cells. A positive linear correlation in TNFmRNA expression was observed between tumor cells and MNCs (r=0.687, P<0.01), a correlation in TNFmRNA and TNF protein expression of tumor cells (r=0.847, P<0.001), and a correlation in TNFmRNA and TNF protein expression of MNC in tumor tissue (r=0.643, P<0.01).
Conclusions: TNFmRNA and TNF protein expression is increased during the development of gallbladder mucosa from hyperplasia, dysplasia to carcinoma, and is increased with tumor stage. This finding suggests that TNF is involved in the pathogenesis of gallbladder carcinoma induced by gallstones and the TNF expression in cancer cells may serve as a marker for tumor stage.