Role of XPA, ERCC1, mtTFA on the survival of patients with metastatic germ cell tumors of testis treated with cisplatin.

5090 Background: Advanced Testis Germ Cell Tumors (TGCT) are treated with platinum based chemotherapy. It has been proposed that DNA repair proteins play a role in the TGCT response to cisplatin. DNA repair deficiencies have been related with better treatment response; such deficiencies could be the result of polymorphisms on DNA repair genes or of the presence of High Mobility Group Proteins B (HMGB). Thus we have investigated whether the presence of XPA, ERCC1 and HMGB (mtTFA), as well as the polymorphism C8092A of the ERCC1 gene may influence the survival of TGCT patients treated with cisplatin.,ERCC1, XPA and mtTFA were detected by immunohystochemistry using tissue microarrays in 58 samples from normal and neoplastic tissue. ERCC1 C8092A polymorphism was determined on DNA isolated from blood and paraffin-embedded tumor samples by PCR/RFLP´S. The results were associated with survival and response.,Only 58 full filled the inclusion criteria. The age-media was 23 years. According to the Royal Marsden stratification, stages IB, II, III and IV showed a frequency of 6.8, 46.5, 8.7 and 38% respectively. The lung (89.7%), mediastine (34.5%) and lymphatic nodes (10.3%) were the most frequent sites for metastases. Prognosis was approached by evaluating three groups: good (25.9%), medium (36.2%) and poor (37.9%). Global survival median was 60 months. Patients presenting samples XPA-negative had a four-years survival of 62% compared to 23% observed in patients (p=0.04). The presence of the A allele of ERCC1 C8092A polymorphism was related with an increased survival (p=0.07). Eighty percent of patients carrying at least one allele A responded to treatment, compared to those individuals with genotype CC, which only 20% of them responded (p=0.023).,This is the first study that evaluates XPA, ERCC1 y mt-TFA in TGCT patients treated with cisplatin. XPA absence was related with a better response to cisplatin-based chemotherapy and an increased survival, suggesting an important role of this protein in the nucleotide excision repair pathway. Carrying the ERCC1 C8092A polymorphic allele promotes resistance to cisplatin treatment in TGCT patients. No significant financial relationships to disclose.