INDUCTION OF MXA MESSENGER-RNA IN PATIENTS WITH NEUROENDOCRINE TUMORSAFTER INTERFERON TREATMENT - LACK OF CORRELATION WITH ANTITUMOR RESPONSE

We have investigated the possibility of using induction of MxA mRNA in patients with neuroendocrine tumors undergoing interferon-alpha (IFN- alpha) treatment as a predictive test for antitumor effect. A total of 122 patients with various types of neuroendocrine tumors were include d in the study. Blood samples were drawn 12 hours after administration of either recombinant or natural IFN-alpha for analysis of induction of MxA mRNA in peripheral blood leukocyte (PBLs). Total RNA was isolat ed and slot-blot hybridization was performed using a MxA cDNA fragment as a probe. All patients displayed induction of MxA mRNA. Out of 13 u ntreated patients, 4 had MxA mRNA as well as 2 out of 11 patients trea ted with somatostatin analogue. All IFN-alpha treated patients showed induction of MxA mRNA and there was no difference between patients dem onstrating partial remisson, stable disease or progressive disease. Mo reover, there was no difference between recombinant or natural leukocy te IFN-alpha in the ability to induce MxA mRNA. Six patients developed neutralizing IFN-alpha antibodies with 1 patient presenting a titre o f 3200 NU/ml. Development of neutralizing antibodies did not abrogate the induction of MxA mRNA, but in 3 patients with high antibody titres the antitumor effect was lost. We therefore conclude that IFN-alpha i s able to induce MxA mRNA in PBLs from patients with neuroendocrine tu mors but we could not find any correlation with the therapeutic outcom e. Furthermore, development of neutralizing IFN-alpha antibodies, alth ough abrogating the antitumor effect, might not block the antiviral ac tivity.