IMPROVED SURVIVAL IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA FAILING 5-FLUOROURACIL WHO RECEIVED IRINOTECAN HYDROCHLORIDE AND HAVE HIGHINTRATUMOR C-FOS EXPRESSION

This study determines the prognostic role of c-fos protein expression in patients with colon cancer who previously failed therapy with 5-flu orouracil (5-FU). Patients with advanced colorectal who were refractor y to 5-FU therapy received irinotecan (CPT-11) by a 90-minute intraven ous infusion at a dose of 125 mg/m(2) weekly for four weeks followed b y a 2-week rest period were eligible for oncogene assessment. C-fos pr otein expression was evaluated using archival formalin-fixed, paraffin -embedded tumor tissue, and an automated immunoperoxidase histochemica l technique. Thirty-five patients were found to have > 25% positive c- fos activity. Nine patients had no detectable c-fos expression. Charac teristics of patient subgroups were not different, however, the median survival of patients with elevated c-fos expression from the time of treatment with CPT-11 was 436 days, whereas patients with no detectabl e c-fos expression had a median survival of 365 days (p = 0.045). C-fo s exhibits a casual role in the initiation of apoptosis and is implica ted in differentiation and proliferation. It has been shown to correla te with poor survival in breast cancer, but improved survival in patie nts with astrocytic glioma. In this analysis, there is a suggestion th at elevated c-fos expression is a good prognostic marker for patients with refractory colorectal carcinoma.