c-KIT mutation analysis for diagnosis of gastrointestinal stromal tumors in fine needle aspiration specimens

Abstract

Background: Gastrointestinal stromal tumors (GISTs) are a specific clinicopathologic entity characterized by activating mutations in the c-KIT gene. These mutations are associated with increased immunohistochemical staining for the c-KIT protein. Because many GISTs display a definitive response to the KIT inhibitor imatinib, accurate diagnosis of these neoplasms is of great clinical importance. GISTs are the most common mesenchymal neoplasms of the digestive tract and show lineage differentiation along the lines of the interstitial cells of Cajal. The cytomorphology of GISTs has been well described, but the cytologic features are not entirely specific and immunohistochemical staining is frequently used to confirm the diagnosis. However, KIT protein positivity established by immunohistochemistry (IHC) may be unreliable in some instances because of a small number of KIT-negative GISTs and immunohistochemical KIT positivity in some non-GIST spindle cell neoplasms of the gastrointestinal tract. Antigen retrieval may be the cause of this spurious positivity. Recently, the demonstration of KIT and PDGFRA mutations has been shown to be more reliable in establishing the diagnosis of GIST than IHC.

Methods: High resolution amplicon melting analysis was performed in a series of eight gastrointestinal stromal tumors sampled by fine needle aspiration (FNA).

Results: In five of eight cases, adequate material was obtained for mutational analysis. In four of these, mutations in the c-KIT gene were detected, and in the fifth case a mutation in the PDGFRA gene was detected.

Conclusions: It appears that high resolution amplicon melting analysis can be successfully performed on material obtained by FNA and will show either KIT for PDGFR mutations in the majority of GIST FNA specimens.