Somatostatin analogues, a series of tissue transglutaminase inducers, as a new tool for therapy of mesenchimal tumors of the gastrointestinal tract.
Imatinib, a tyrosine kinase inhibitor directed against the enzymatic domain of KIT protein, was found to produce dramatic clinical responses in metastatic gastrointestinal stromal tumors (GISTs). However, resistance usually develops thus determining treatment failure. The present study was performed to analyse the expression of somatostatin receptor (SSTR) subtypes, modulators of tissue transglutaminase, in a series of GISTs and leiomyosarcomas by immunohistochemistry to identify a new potential therapeutic target. Sixteen cases (8 males and 8 females, age range: 38-73; 11 GISTs, 4 leiomyosarcomas, 1 leiomyoma) were studied. Immunohistochemical detection of the relevant SSTRs was performed on paraffin-embedded tissue sections, stained with polyclonal antibodies directed against the five somatostatin receptor subtypes. We found 7 out of 16 (44%) tumors 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 exhibiting an intense labeling in most of these cases. The significant expression of SSTRs shown in this series of GISTs and gastrointestinal leiomyosarcomas 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.
Palmieri
G
G
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy. giovannella.palmieri@email.it
Montella
L
L
Aiello
C
C
Barbieri
F
F
Di Vizio
D
D
Schulz
S
S
Beninati
S
S
Budillon
A
A
Caraglia
M
M
Insabato
L
L
Florio
T
T
D000328:Adult; D000368:Aged; D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D007889:Leiomyoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008648:Mesoderm / Q000201:enzymology / Q000473:pathology; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000096:biosynthesis; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011503:Transglutaminases / Q000096:biosynthesis*
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D017481:Receptors, Somatostatin; D013004:Somatostatin; D000068877:Imatinib Mesylate; D011503:Transglutaminases; D019009:Proto-Oncogene Proteins c-kit