BACKGROUND: Some reports have confirmed that occur-rence and development of tumor are related with lots of on-cogene, anti-oncogene and cytokine. This study was to de-tect the expression of TNFmRNA, tumor necrosis factor(TNF) and TNF receptor (TNFR) in the gallbladder mu-cosa which developed from hyperplasia, dysplasia to carci-noma , and to further discuss the pathogenecity of gallblad-der carcinoma.METHODS: The expression of TNFmRNA, TNF and TN-FR was detected by in situ hybridization and immunohisto-chemistry on the surgical specimens of hyperplasia, dyspla-sia and carcinoma of the gallbladder.RESULTS: The percentage of positive cells expressed TNF-mRNA 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 carci-noma of gallbladder tissues was 15%, 85%, and 90%, re-spectively (P<0.05). The number of positive MNC high-power field ( Hpf) was 4.85 ±1.50, 6.00±2.71, and9.33 ±3.07, respectively (P<0.05). The number of carci-noma 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 andwas 9.13 ±4.39 and 7.13 ±2.53 (P<0.05), and that ofMNC/Hpf was 14.80 ±4.02 and 11.10 ±2.23 (P<0.01).The number of carcinoma cells and MNCs expressed byTNFmRNA per Hpf was increased with the increase oftumor size. In tumors of more than 2 cm or less than 2 cmin diameter, the number of positive carcinoma cells/Hpfwas 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 similarto that of TNFmRNA, whereas TNF protein expressionwas more frequent and extensive than TNFmRNA expres-sion. TNFR was expressed in endothelial cells and MNCs ofcarcinoma, and was negative in mucosal epithelial cells andtumor cells. A positive linear correlation in TNFmRNA ex-pression was observed between tumor cells and MNCs(r =0.687, P <0.01), a correlation in TNFmRNA and TNFprotein expression of tumor cells (r =0.847, P<0.001),and a correlation in TNFmRNA and TNF protein expres-sion of MNC in tumor tissue (r =0.643, P <0.01).CONCLUSIONS: TNFmRNA and TNF protein expressionis increased during the development of gallbladder mucosafrom hyperplasia, dysplasia to carcinoma, and is increasedwith tumor stage. This finding suggests that TNF is in-volved in the pathogenesis of gallbladder carcinoma in-duced by gallstones and the TNF expression in cancer cellsmay serve as a marker for tumor stage. BACKGROUND: Some reports have confirmed that occur-rence and development of tumors are related with lots of on-cogene, anti-oncogene and cytokine. This study was to de-tect the expression of TNF mRNA, tumor necrosis factor (TNF) and TNF receptor (TNFR) in the gallbladder mu-cosa which developed from hyperplasia, dysplasia to carci-noma, and further to discuss the pathogenecity of gallblad-der carcinoma. METHODS: The expression of TNFmRNA, TNF and TN-FR was detected by in situ hybridization and immunohisto-chemistry on the surgical specimens of hyperplasia, dysplasia and carcinoma of the gallbladder .RESULTS: The percentage of positive cells expressed TNF-mRNA in the gallbladder mucosa was 0%, 20%, and 90%, respectively in hyperplasia, The percentage of positive mononuclear cells (MNCs) expressed TNF mRNA in hyperplasia, dysplasia and carci-noma of gallbladder tissues was 15%, 85%, and 90%, re-spectively (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 carci-noma cells and MNCs expressed by TNFm per high-power field was increased with the increase of tumor stage The number of carcinoma cells / Hpf in stages and 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 In tumors of more than 2 cm or less than 2 cmin diameter, the number of positive carcinoma cells / Hpfwas 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 similarto that of TNF mRNA, whereas TNF protein expression was more frequent and extensive than that of TNF mRNA expres- sion. 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 exa correlation in TNF mRNA and TNF protein expression of tumor cells (r = 0.847, P <0.001), and a correlation in TNF mRNA and TNF protein expres-sion (r = 0.687, of MNC in tumor tissue (r = 0.643, P <0.01) .CONCLUSIONS: TNF mRNA and TNF protein expression increased during the development of gallbladder mucosafrom hyperplasia, dysplasia to carcinoma, and is increasedwith tumor stage. This finding suggests that TNF is in-volved in the pathogenesis of gallbladder carcinoma in-duced by gallstones and the TNF expression in cancer cells may serve as a marker for tumor stage.