Loss of RKIP expression is associated with poor survival in GISTs

Abstract

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours of the digestive tract and are commonly driven by oncogenic mutations in KIT and PDGFRA genes. Tumour size, location, mitotic index and KIT/PDGFRA mutations are the most important prognostic parameters in GISTs. However, additional studies screening for new molecular prognostic markers in GISTs are missing. Raf kinase inhibitor protein (RKIP) has been considered as a suppressor of metastasis and a prognostic marker in several neoplasms. In the present study we aimed to examine whether RKIP expression is associated with GIST clinical-pathological features. Using immunohistochemistry, we determined RKIP expression levels in a well-characterised series of 70 GISTs. We found that RKIP is expressed in the great majority of cases, and absent in approximately 9% of GISTs. Additionally, we found that loss of RKIP expression was not due to the promoter methylation as assessed by methylation-specific PCR. Loss of RKIP expression was associated with poor disease-specific survival and with tumour necrosis in GISTs. Furthermore, a statistical tendency was observed between the positive RKIP expression and absence of metastasis. So far, this is the first study assessing RKIP expression levels in GISTs. We conclude that loss of RKIP expression could have an important role as prognostic marker in GISTs.