Einfluss der Oberflächenmarkerexpression auf Leukozyten von Hodentumorpatienten in fortgeschrittenen Stadien auf das rezidivfreie Überleben nach Hochdosischemotherapie und autologer Stammzelltransplantation

Testicular cancer is the most common tumor in 15 to 45 year old men. Even in advanced stages it has a quite good prognosis with a survival rate of about 70-80%. In order to better estimate the prognosis of those patients with metastatic or relapsed disease the International Germ Cell Collaborative Group has developed a score (IPF-score). In the last years a lot of research on the field of tumorimmunology has been done. In Non-small cell lung cancer proteins that are part of the leukocyte adhesion pathway have a significant influence on the relapse probability of the patients. Furthermore the enzyme β-1,4-galactosyltransferase was found to be significantly higher in patients who do not suffer a relapse of disease. In testicular germ cell tumors little is known about tumorimmunologic interactions so far. Besides most of the studies have investigated the expression levels on the tumor cells themselves. In this paper we tested them on the patients´ leucocytes. This study was supposed to investigate the influence of B4GALT1, as well as different surface molecules, which are part of the leucocytes adhesion pathway, on the relapse probability of the patients. Three different surface markers were chosen for analysis. Those were platelet endothelial cell adhesion molecule 1 (PECAM1), very late antigen 4 (VLA-4) and CXC receptor 4 (CXCR4). Furthermore we measured the expression of IL10, which has impact on tumor control because of immunoregulatory functions. All of the 46 patients received high-dose chemotherapy and autologous stem cell transplantation. During stem cell apheresis retention samples were taken. Patients had given written informed consent in research usage of the samples. The surface expression levels of PECAM-1, VLA-4 and CXCR4 were measured with flow cytometry. Moreover T-cells and monocytes were separated from the other cells. Afterwards RNA was extracted from all cells in order to determine mRNA-expression levels of B4GALT1 and IL10 with real time-polymerase chain reaction (RT-PCR). For analysis the IPF-score of all patients was calculated and patients were grouped according to the further course of disease into the groups “no relapse”, “early relapse” and “late relapse”. The analysis of the surface marker expression levels did not show any significant differences between the groups neither for T-cells nor for monocytes. Whereas the expression of B4GALT1 was significantly higher in T-cells of patients without relapse compared to the other groups. In monocytes and the all cell-population no differences were found. Kaplan-Meier analysis showed that patients with a high B4GALT1 expression in T-cells had a longer relapse-free survival. This study was conducted with a limited number of thawed patient samples. For validation of the results, further studies, such as prospective trials, are needed.