title: Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs.
abstract: Somatostatin analogs (SSA) are the standard diagnostic and treatment tools in the clinical management of patients with neuroendocrine tumors (NETs) expressing somatostatin receptors (SSTRs). Although symptomatic and biochemical control is obtained with SSA in the majority of functional NETs, antineoplastic effects of SSA are partial and of limited duration. The aim of this study was to quantify expression levels of five SSTR subtypes (SSTR1-SSTR5) and correlate them with the clinical outcomes of patients with NETs who underwent SSA therapy. The expression levels were analyzed using real-time polymerase chain reaction in a series of 22 metastatic NETs with a median time of 10 months on the SSA therapy (range 2-82 months). The median duration of disease stabilization in patients who developed progression (n = 14) was 9 months (range 3-92 months). The median survival period for all patients was 44 months (range 3-175 months). According to RECIST criteria, one (5%) partial objective tumor response was obtained, disease stabilization was achieved in 10 (45%) patients, and progressive disease was observed in 11 (50%). Analysis of mRNA expression of the SSTR subtypes showed that SSTR2 and SSTR5 were expressed in all of the studied NETs; SSTR1 and SSTR4 in all but 3 tumors (86%); and SSTR3 in only 10 NETs (49%). Interestingly, our preliminary data suggest that only the levels of SSTR4, though it has the lowest affinity for SSA of all SSTR subtypes, were significantly associated with the stabilization of disease during SSA therapy (p = 0.0357). These levels correlated with time to progression (p = 0.0015) and overall survival (p = 0.0017) in NET patients.
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. slaby@mou.cz
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
authors.forename: Milana
authors.initials: M
authors.lastname: Sachlova
authors.forename: Marketa
authors.initials: M
authors.lastname: Bednarikova
authors.forename: Pavel
authors.initials: P
authors.lastname: Fabian
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.forename: Simona
authors.initials: S
authors.lastname: Vytopilova
authors.forename: Dalibor
authors.initials: D
authors.lastname: Valik
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007205:Indium Radioisotopes; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008479:Mediastinal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015282:Octreotide / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics; D017481:Receptors, Somatostatin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007205:Indium Radioisotopes; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; D015282:Octreotide