Abstract
ABSTRACTPurpose:Testicular germ cells tumor (TGCT) are associated with a high cure rate and are treated with platinum-based chemotherapy. However, a group of testicular cancer patients may have a very unfavorable evolution and insensitivity to the main therapeutic agent chemotherapy (CT) cisplatin. The aim of this study was to evaluate the risk of recurrence and overall survival related to the expression of nuclear factor kappa-B (NF-κB), transglutaminase 2 (TG2) and excision repair cross-complementation group 1 (ERCC1) in patients with TGCT treated with platinum combinations.Patients and Methods:A retrospective study was performed with TGCT patients treated with platinum-based chemotherapy. Immunohistochemical analysis was performed and the expression was correlated with clinical and laboratory data.Results:Fifty patients were included, the mean age was 28.4 years (18 to 45), and 76% were non-seminoma. All patients were treated with standard cisplatin, etoposide and bleomycin or cisplatin, and etoposide. Patient’s analyzed immunodetection for NF-κB, TG2, and ERCC1 were positive in 76%, 54% and 42%, respectively. Multivariate analysis identified that positive expressions to ERCC1 and NF-κB are independent risk factors for higher recurrence TGCT after chemotherapy (RR 2.96 and 3.16, respectively). Patients with positive expression of ERCC1 presented a poor overall survival rate for 10-year follow (p=0.001).Conclusions:The expression of ERCC1 and NF-κB give a worse prognosis for relapse, and only ERCC1 had an influence on the overall survival of TGCT patients treated with platinum-based chemotherapy. These may represent markers that predict poor clinical outcome and response to cisplatin.
Highlights
Testicular tumors account for 1% of all cancers in men
One of the main problems related to the recurrence of testicular germ cell tumors (TGCT) is platinum resistance and the mechanisms associated with cisplatin resistance involve many different cellular
Our results showed that the expression of excision repair cross-complementation group 1 (ERCC1) is associated with increased risk for TGCT relapse after treatment with platinum-based chemotherapy
Summary
Testicular tumors account for 1% of all cancers in men. It is most frequent in men 1535 years old and involves always a dramatic diagnosis [1]. Cisplatin cytotoxic activity results of interactions with DNA and the inability to repair DNA strand can lead to tumor cell apoptosis [3,4,5]. Adducts between platinum and DNA inhibit cellular processes, such as replication, transcription, translation and DNA repair [3]. Cisplatin binding to the mitochondrial DNA leads to decreased ATP and the decrease in ATPase activity and modification of the calcium content [4]
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