Somatostatin receptor expression in stromal tumors of the gastrointestinal

Background: Imatinib mesylate (STI-571, Gleevec) a small molecule tyrosine kinase inhibitor directed against the enzymatic domain of KIT protein, was recently found to produce dramatic clinical responses as monotherapy for metastatic GISTs. However, imatinib resistance can occur determining treatment failure. The present study was performed to analyse the expression of somatostatin receptor (SSTR) subtypes in a series of Gastrointestinal (GI) stromal tumors by immunohistochemistry and possibly identify an additional therapeutic target. Methods: Sixteen cases of GI stromal tumors (8 males and 8 females, age range: 38–73) were studied. 11 GISTs, 4 leiomyosarcomas, 1 leiomyoma were included. A gastric leiomyosarcoma was doubly evaluated (primitive tumor and metastatic lung lesion). Immunohistochemical detection of SSTRs was performed on sections (4μm) of paraffin-embedded tissue stained with polyclonal antibodies directed against the five somatostatin receptor subtypes. Results: We found 7 out of 16 tumors (44%) expressing all SSTRs and 14 out of 16 (87%) tumors positive for at least 3 subtypes. SSTR2A was the most represented subtype in the tumors studied, being expressed in approximately 70% of cases and usually exhibiting an intense labeling. All GISTs apart one resulted positive for more than two SSTR subtypes. SSTR2A was the most strongly expressed subtype in GISTs (72% of cases). All 4 leiomyosarcomas of this series expressed SSTRs, being SSTR4 and SSTR5 positive in all cases. Conclusions: The significant expression of SSTRs showed in this series of GI stromal tumors suggests a potential therapeutic target to be explored alone and/or in combination with other therapeutic agents in the setting of refractory GI stromal tumors.