Die Expression von Metallothionein und Glutathion im Tumorgewebe von Ovarialkarzinomen

Abstract

Purpose: Metallothioneins (MT) are small cysteine-rich proteins. Together with glutathione (GSH) they constitute the major fractions of intracellular thiols. Since MT as well as GSH have been reported to protect tumor cells from anti-neoplastic agents both thiols may play a role in drug resistance. In the present study, MT and GSH expression was determined in primary epithelial ovarian carcinomas and a possible association with histopathological parameters and survival time (differentiating between patients with and without standard chemotherapy) was examined. Material and Methods: Glutathione expression as well as expression of MT isoforms (MT-1 and MT-2) was determined in 151 patients suffering from primary epithelial ovarian cancer. Results: No association between MT or GSH expression and survival was observed in patients that received platinum-based chemotherapy. However, an interesting result was obtained by combined analysis of MT and total GSH content. The product of MT and GSH was negatively associated with survival of grade 1 carcinomas (p = 0.021, log-rank test). When MT x GSH was greater than the median 25% of patients with grade 1 carcinomas died within 235 days. In contrast, all patients with grade 1 carcinomas survived when MT x GSH in tumor tissue was smaller than the median. No influence of MT, GSH or MT x GSH on survival was observed for patients with grade 2 or grade 3 carcinomas. This szenario suggests that high expression of MT and GSH give a growth and/or selection advantage to grade 1 carcinomas, wheras other factors seem to be responsible for progression of grade 2 and 3 carcinomas. Conclusion: High expression of both sulfhydryl factors MT and GSH may identify a subgroup of low-grade carcinomas with an increased risk of progression.