CCNE1 and gastrointestinal stromal tumor: However, immunohistochemical positivity of cyclin A, cyclin B, cyclin D1, cyclin E and cdc2 [17,19,20] or the loss of cyclin kinase inhibitors p27 and p21 [16-18,25-27] has only been shown to be associated with high risk grading in GIST, while investigations in regard to clinical outcome are missing.