• Pilar Blay, Aurora Astudillo, José M Buesa, Elías Campo, Mar Abad, Juan García-García, Rosa Miquel, Vicente Marco, Marta Sierra, Raquel Losa, Angel Lacave, Alejandro Braña, Milagros Balbín, and José M P Freije.
• Servicios de Oncología Médica, Anatomía Patológica, and Traumatología, Instituto Universitario de Oncología, Hospital Central de Asturias, Oviedo, Spain.
• Clin Cancer Res. 2004 Jun 15; 10 (12 Pt 1): 4089-95.

PurposeGastrointestinal 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.Experimental DesignBy 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.ResultsWe 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.ConclusionsOur 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.

37 keywords...

hide…