The Study Of Hypoxia State And Its Significance Of Gastric Carcinoma During Progression And Heterogeneity

Objective To explore the loss of heterozygosity(LOH) of the SDHD gene in mitochondria and the morphological features of the expression of cytochrome C(cyt C)and HIF-1a in gastric carcinomas so as to understand the state of hypoxia in gastric carcinomas during their progression and heterogeneity and to study the significance of it and its relationship with the progression and heterogeneity of tumors.Method 1)Using PCR-LOH analysis(SSLP) method , we examined the LOH of the three microsatellites:D11S5017,D11S1347 and D11S1328 closely around the SDHD gene in 35 cases of fresh gastric carcinomas(includes middle and low differential adenocarcinoma and mucoid adenocarcinoma, et al) 2) Using immunohistochemistry, we examined the expression of cytochrome C and HIF-1a in 50 cases of paraffin embedded gastric carcinomas and their paratumor tissues.The results were analyzed by statistics methods-t test,chi-square and exact probabilistic method.Respite There were nonrandom LOH of the SDHD gene sites in the gastric carcinoma tissues/The total of LOH in the three sites was 19.35%(6/31).The mean light density of the expression of cytochrome C in normal tussue was 0.41048, while that in the gatric carcinoma tissue was 0.2067683, and the difference between them was highly significant(p<0.01).What's more,there were, also highly significant differences in all other groups(p<0.01).There were no expression of HIF-1a in the normal tissues .while the positive rate of HIF-1a in gastric carcinoma was 44%(22/50). HIF-1a was mainly expressed in the nuclear and plasm of the cancer cells. The difference of the positive rate of the HIF-1a was statistical significant(p<0.05) among different differential gastric carcinoma groups and HBF-1a expression was also associated with the condition of metastasis of the lymph nodes. Both expression of them has evident heterogeneity in different gastric carcinoma tissues and in different cells in the same tumors. In addition, both expression of cytochrome C and HIF-1a in the LOH positive group are stronger than those in LOH negative group and the different was statistical significant(p<0.05).Conclusion 1)There are LOH of SDHD gene in the gastric carcinomas and so it can be considered as a special type of tumor suppressor that coded by nuclear genes .The gene alteration of it may more or less restrain the function of aerobic respiratory in mitochondria and take part in the so-called "active hypoxia".What's more this will become more severe as the progression and heterogeneity of tumors.. 2) The expression of cytochrome C in gastric carcinomas is positively associated with the differentiation of gastric carcinomas that is as tumor become higher malignant and more aggressive, its respiratory function will be more suppressed. The lower of differentiation of tumor the...