title: Protein kinase C theta is highly expressed in gastrointestinal stromal tumors but not in other mesenchymal neoplasias.
abstract: OBJECTIVE
  Gastrointestinal stromal tumors (GIST) are a distinctive group of mesenchymal neoplasms of the gastrointestinal tract. The oncogene KIT has a central role in the pathogenesis of GIST, with c-kit receptor tyrosine kinase (KIT) protein expression being the gold standard in its diagnosis. The identification of GIST patients has become crucial, because the tyrosine kinase inhibitor Imatinib is effective in the treatment of this malignancy. However, a small set of GISTs remain unrecognized, because KIT protein expression is not always evident. The aim of this study was the identification of new markers for the differential diagnosis of GIST.
  
  
  METHODS
  By analyzing publicly available data from transcriptional profiling of sarcomas, we found that protein kinase C theta (PKC-theta), a novel PKC isotype involved in T-cell activation, is highly and specifically expressed in GIST. PKC-theta expression in GIST was confirmed by reverse transcription-PCR and Western blot. PKC-theta was analyzed by immunohistochemistry in a panel of 26 GIST, 12 non-GIST soft-tissue sarcomas, and 35 tumors from other histologies.
  
  
  RESULTS
  We found that all of the GISTs expressed PKC-theta, whereas this protein was undetectable in other mesenchymal or epithelial tumors, including non-GIST KIT-positive tumors. PKC-theta immunoreactivity was also observed in interstitial cells of Cajal.
  
  
  CONCLUSIONS
  Our results show that PKC-theta is easily detected by immunohistochemistry in GIST specimens and that it could be a sensitive and specific marker for the diagnosis of this malignancy.
authors.affiliation: Servicios de Oncología Médica, Anatomía Patológica, and Traumatología, Instituto Universitario de Oncología, Hospital Central de Asturias, Oviedo, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Blay
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: José M
authors.initials: JM
authors.lastname: Buesa
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
authors.forename: Mar
authors.initials: M
authors.lastname: Abad
authors.forename: Juan
authors.initials: J
authors.lastname: García-García
authors.forename: Rosa
authors.initials: R
authors.lastname: Miquel
authors.forename: Vicente
authors.initials: V
authors.lastname: Marco
authors.forename: Marta
authors.initials: M
authors.lastname: Sierra
authors.forename: Raquel
authors.initials: R
authors.lastname: Losa
authors.forename: Angel
authors.initials: A
authors.lastname: Lacave
authors.forename: Alejandro
authors.initials: A
authors.lastname: Braña
authors.forename: Milagros
authors.initials: M
authors.lastname: Balbín
authors.forename: José M P
authors.initials: JM
authors.lastname: Freije
mesh_terms: D001549:Benzamides; D015153:Blotting, Western; D005770:Gastrointestinal Neoplasms / Q000201:enzymology*; D005786:Gene Expression Regulation; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008648:Mesoderm / Q000201:enzymology*; D009369:Neoplasms / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000096:biosynthesis*; D000074121:Protein Kinase C-theta; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology*; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001549:Benzamides; D007527:Isoenzymes; D010879:Piperazines; D020033:Protein Isoforms; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta