Protein kinase C theta is highly expressed in gastrointestinal stromal tumors but not in other mesenchymal neoplasias.
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.
Blay
Pilar
P
Servicios de Oncología Médica, Anatomía Patológica, and Traumatología, Instituto Universitario de Oncología, Hospital Central de Asturias, Oviedo, Spain.
Astudillo
Aurora
A
Buesa
José M
JM
Campo
Elías
E
Abad
Mar
M
García-García
Juan
J
Miquel
Rosa
R
Marco
Vicente
V
Sierra
Marta
M
Losa
Raquel
R
Lacave
Angel
A
Braña
Alejandro
A
Balbín
Milagros
M
Freije
José M P
JM
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
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