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

The aim of this study was to evaluate the antiproliferative effects of inte rferon alpha (IFN-alpha) on neuroendocrine differentiated cell lines and, r etrospectively, to assess the prognostic significance of p68 protein kinase (PKR) induction in neuroendocrine gut and pancreatic tumour patients. Arch ive specimens from 56 patients were studied, 43 before IFN-alpha and 56 dur ing therapy. The tissues were immunostained for p68 protein kinase (PKR) us ing the monoclonal antibody (MAb) TJ4C4. A significant increase in immunost aining after treatment with IFN-alpha compared with before treatment (3.47/-0.12 versus 2.72 +/- 0.15, P<0.001) was noted. The p68 scare was signific antly 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 wit h 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). F urthermore, IFN-alpha showed a significant antiproliferative effect (by [H- 3]thymidine incorporation) on two carcinoid tumour cell lines in a dose-dep endent maimer which correlated with a dose-dependent induction of p68 mRNA and protein expression (by Northern and Western blot analysis). We conclude that IFN-alpha can effectively inhibit the in vitro growth carcinoid tumor cell lines and upregulates the expression of p68 at both rRNA and protein levels in carcinoid tumours. The induction of p68 could be a prognostic ind icator of response in patients with carcinoid tumours during IFN-alpha trea tment. (C) 1998 Elsevier Science Led, All rights reserved.