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Protein Kinase C Is Highly Expressed in Gastrointestinal Stromal Tumors But Not in Other Mesenchymal Neoplasias

¹ Servicios de Oncología Médica, ² Anatomía Patológica, and ³ Traumatología, Instituto Universitario de Oncología, Hospital Central de Asturias, Oviedo; ⁴ Laboratorio de Patología, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona; ⁵ Departamento de Biología Celular y Patología, Universidad de Salamanca, Salamanca; ⁶ Servicio de Anatomía Patológica, Hospital General de Catalunya, Barcelona; and ⁷ Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain

Purpose: 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.

Experimental Design: By analyzing publicly available data from transcriptional profiling of sarcomas, we found that protein kinase C (PKC-), a novel PKC isotype involved in T-cell activation, is highly and specifically expressed in GIST. PKC- expression in GIST was confirmed by reverse transcription-PCR and Western blot. PKC- 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-, whereas this protein was undetectable in other mesenchymal or epithelial tumors, including non-GIST KIT-positive tumors. PKC- immunoreactivity was also observed in interstitial cells of Cajal.

Conclusions: Our results show that PKC- is easily detected by immunohistochemistry in GIST specimens and that it could be a sensitive and specific marker for the diagnosis of this malignancy.

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