NAD(P)H: Quinone oxidoreductase (NQO1) and catalase expression in nonseminomatous germ cell tumors.

Abstract

413 Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme which detoxifies quinones and reduces oxidative stress. NQO1 is expressed in multiple tumor types at levels up to 200-fold above normal tissue, including in breast, pancreatic, and non-small cell lung cancers. NQO1 bioactivatable drugs have the potential to deliver tumor-selective DNA damage and cell death by exploiting the elevation of NQO1. Alterations in catalase expression can cause marked cytoprotection. The ratio of NQO1:catalase activities is presumed to be a predictive marker for therapeutic activity of NQO1 bioactivatable drugs. There is no data available on NQO1 and catalase expression in germ cell tumors. Methods: Patients with germ cell tumor who underwent orchiectomy/tumor resection between January 2016 and December 2018 were identified from the Indiana University Melvin and Bren Simon Cancer Center database. Patients with non-seminomatous germ cell tumor of testis or primary mediastinal non-seminomatous germ cell tumor were selected. Immunohistochemistry staining for NQO1 and catalase was performed on tumor tissue. Results: NQO1 and catalase expression were assessed in 16 patients. Fifteen of 16 tumors stained positive for NQO1, 13 of which were moderately to strongly positive. Conversely, the majority of tumors were catalase deficient or only mildly positive for catalase. The details of the Immunostaining is summarized in the table below. Conclusions: Non-seminomatous germ cell tumors appear to have overexpression of NQO1 and deficiency of catalase. NQO1 bioactivatable agents could be beneficial in treating patients with refractory non-seminomatous germ cell tumors.[Table: see text]