title: High CD133 expression levels in gastrointestinal stromal tumors.
abstract: BACKGROUND
  Gastrointestinal stromal tumours (GISTs) have activating KIT or PDGFRA gene mutations. Imatinib mesylate, which targets KIT and PDGFRA, is effective in treating GISTs, but 90% of GIST patients become imatinib-resistant as a result of acquiring secondary KIT mutations. Recent findings suggest that tumour growth can be driven by mutated self-renewing progenitors known as cancer stem cells (CSCs), which are believed to be present in all neoplastic proliferations and are thought to accumulate mutations. It is therefore possible that the acquisition of secondary KIT mutations during imatinib treatment may occur in putative GIST CSCs.
  
  
  METHODS
  Using flow cytometry, in vivo murine xenografts and molecular characterization, we tried to identify putative GIST CSCs by looking for the occurrence of common CSC markers such as KIT, CD133, CD90, CD44, and CD34 in 18 surgical samples obtained from nine untreated and nine imatinib-treated KIT-mutated GIST patients.
  
  
  RESULTS
  The results indicated the homogeneous and previously unreported expression of CD133 (18/18), CD90 (15/16), and CD44 (12/14), together with KIT (18/18) and CD34 (13/18). This profile is similar to that identified in bone marrow mesenchymal progenitors and does not seem to be significantly modified by imatinib as only marginal changes in KIT and CD133 expression (P ≤ 0.05, Mann-Whitney test) were found in the treated samples.
  
  
  CONCLUSIONS
  These findings suggest that GISTs are a clonal expansion of quite primitive cells that strictly depend on KIT oncogenic addiction, and have no cancer/stem cell component that can be detected by means of the antigens used in this study.
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bozzi
authors.forename: Elena
authors.initials: E
authors.lastname: Conca
authors.forename: Giacomo
authors.initials: G
authors.lastname: Manenti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Negri
authors.forename: Silvia
authors.initials: S
authors.lastname: Brich
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides; D002460:Cell Line; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D001549:Benzamides; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D010879:Piperazines; C000606024:Prom1 protein, mouse; D011743:Pyrimidines; D018800:Thy-1 Antigens; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit