Loss of RKIP expression is associated with poor survival in GISTs |
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Authors: | Olga Martinho António Gouveia Paula Silva Amadeu Pimenta Rui Manuel Reis and José Manuel Lopes |
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Institution: | 1.Life and Health Sciences Research Institute (ICVS), School of Health Sciences,University of Minho,Braga,Portugal;2.IPATIMUP,Institute of Molecular Pathology and Immunology of the University of Porto,Porto,Portugal;3.Department of Surgery,Porto,Portugal;4.Department of Pathology, H.S. Jo?o,Porto,Portugal;5.Medical Faculty of Porto University,Porto,Portugal |
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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. |
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