| Autor: |
Mego M; 2nd Department of Oncology, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia.; Translation Research Unit, National Cancer Institute, Comenius University, Bratislava, Slovakia.; Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia., Kalavska K; Translation Research Unit, National Cancer Institute, Comenius University, Bratislava, Slovakia., Horak S; Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Hyblova M; Medirex Group Academy n.p.o., Nitra, Slovakia., Kolnikova G; Department of Pathology, National Cancer Institute, Bratislava, Slovakia., Novotna V; 1st Department of Oncology, Faculty of Medicine, Comenius University, St. Elisabeth Cancer Institute, Bratislava, Slovakia., Majtanova K; Translation Research Unit, National Cancer Institute, Comenius University, Bratislava, Slovakia.; Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia., Minarik G; Medirex Group Academy n.p.o., Nitra, Slovakia., Kucerova L; Translation Research Unit, National Cancer Institute, Comenius University, Bratislava, Slovakia.; Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia., Cierna Z; Department of Pathology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.; Department of Pathology, Faculty Hospital, Trnava, Slovakia. |
| Abstrakt: |
Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs. |
