Abstract
BackgroundMolecular analyses of the c-kit and PDGFRα genes have contributed greatly to our understanding of the development of gastrointestinal stromal tumors (GISTs), but little is known about their malignant potential. The aim of our study was to evaluate cell cycle regulators as potential prognostic markers in GISTs.MethodsWe investigated 104 KIT positive GISTs from various tumor sites in immunoassays on CD34, Ki67 and particularly on P53, BCL-2 and Cyclin D1. The results were compared with tumor size, mitotic rate, proliferative activity, histological subtype, nuclear atypia and risk assessment according to Fletcher and Miettinen. Occurrence of metastases and survival were also taken into account.ResultsThe expression of P53 was significantly correlated with high risk criteria towards malignancy and epithelioid differentiation in GISTs. Likewise P53 label correlated significantly with the established prognostic indicators: tumor size, mitotic rate, nuclear atypia and proliferative activity. Regarding the site of tumor presentation, P53 was not a decisive factor. BCL-2 and Cyclin D1 expression was not related to any of the prognostic indicators.ConclusionThe present data identified P53 being a recommendable marker for predicting the risk of malignancy in GISTs. In addition, we found P53 significantly correlated with epithelioid tumor differentiation, independent of tumor site. BCL-2 and Cyclin D1, however, did not prove to be deciding markers for diagnosis and prognosis.
Highlights
Molecular analyses of the c-kit and PDGFRα genes have contributed greatly to our understanding of the development of gastrointestinal stromal tumors (GISTs), but little is known about their malignant potential
Beside KIT, CD34 and Ki67 antigen, we investigated the expression of P53, BCL-2, and Cyclin D1
Pure or predominantly epithelioid differentiation with polygonal tumor cells containing clear cytoplasm was found in 37 GISTs (36%)
Summary
Molecular analyses of the c-kit and PDGFRα genes have contributed greatly to our understanding of the development of gastrointestinal stromal tumors (GISTs), but little is known about their malignant potential. The aim of our study was to evaluate cell cycle regulators as potential prognostic markers in GISTs. In recent years, progress has been achieved in establishing accurate diagnoses of gastrointestinal stromal tumors (GISTs), elucidating their molecular pathogenesis and developing a specific treatment. BMC Cancer 2008, 8:204 http://www.biomedcentral.com/1471-2407/8/204 factor receptor alpha (PDGFRα) [1,2,3]. Mutations in both genes lead to ligand independent dimerization of transmembrane tyrosine kinase receptor type III and to intracytoplasmic signal transduction via phosphorylation of tyrosine kinase [4,5,6,7]. Epithelioid GISTs have been described with a variable nest-like, trabecular and pleomorphic differentiation [9]
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