Progress in molecular diagnostics of gastrointestinal stromal tumors

Gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal tumor of the alimentary tract, presently being defined as a tumor composed of spindle and/or epithelioid cells presumably differentiating towards interstitial cells of Cajal. The most frequent location of gastrointestinal stromal tumor is the stomach, followed by other sites of gastrointestinal tract. Occasional sites of occurrence are mesenterium, omentum, retroperitoneum, gall bladder, urinary bladder, pancreas, prostate and the vagina. Most of these tumors are KIT-immunoreactive and almost all carry mutated KIT or PDGFRA genes encoding two transmembrane class III tyrosine kinases. These mutations not only shed light on molecular oncogenesis of GISTs, but can also serve as diagnostic markers of this type of tumor, and, last but not least, the function of the proteins encoded by the mutated genes may be influenced by small molecule tyrosine kinase inhibitors. Nevertheless, negative results of immunohistochemistry and mutational analysis do not exclude histologically proven diagnosis of GIST, and although the response to tyrosine kinase inhibitors is correlated with the presence and type of KIT and PDGFRA mutations, the molecular genetic analysis of these genes is presently not required for imatinib therapy of GISTs.