Expression of p68 protein kinase and its prognostic significance during IFN-α therapy in patients with carcinoid tumours

The aim of this study was to evaluate the antiproliferative effects of interferon alpha (IFN-α) on neuroendocrine differentiated cell lines and, retrospectively, to assess the prognostic significance of p68 protein kinase (PKR) induction in neuroendocrine gut and pancreatic tumour patients. Archive specimens from 56 patients were studied, 43 before IFN-α and 56 during therapy. The tissues were immunostained for p68 protein kinase (PKR) using the monoclonal antibody (MAb) TJ4C4. A significant increase in immunostaining after treatment with IFN-α compared with before treatment (3.47±0.12 versus 2.72±0.15, P<0.001) was noted. The p68 score was significantly increased after treatment only in patients with stable disease before=2.71±0.19, after=3.40±0.14 (P<0.001) or an objective response before 3.13±0.22, after=4.00±0.24 (P<0.05) but not in those with progressive disease (before=2.32±0.24, after 2.86±0.26, NS). A low p68 score (<3.0) during treatment was a predictor of shorter duration of response and overall survival (P=0.0062 and P<0.0001, respectively). Furthermore, IFN-α showed a significant antiproliferative effect (by [³H]thymidine incorporation) on two carcinoid tumour cell lines in a dose-dependent manner which correlated with a dose-dependent induction of p68 mRNA and protein expression (by Northern and Western blot analysis). We conclude that IFN-α can effectively inhibit the in vitro growth of carcinoid tumor cell lines and upregulates the expression of p68 at both mRNA and protein levels in carcinoid tumours. The induction of p68 could be a prognostic indicator of response in patients with carcinoid tumours during IFN-α treatment.