Blay Pilar, Astudillo Aurora, Buesa José M, Campo Elías, Abad Mar, García-García Juan, Miquel Rosa, Marco Vicente, Sierra Marta, Losa Raquel, Lacave Angel, Braña Alejandro, Balbín Milagros, Freije José M P
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. doi: 10.1158/1078-0432.CCR-04-0630.
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.
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.
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.
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.
胃肠道间质瘤（GIST）是胃肠道中一组独特的间充质肿瘤。致癌基因KIT在GIST的发病机制中起核心作用，c-kit受体酪氨酸激酶（KIT）蛋白表达是其诊断的金标准。GIST患者的识别变得至关重要，因为酪氨酸激酶抑制剂伊马替尼对这种恶性肿瘤有效。然而，一小部分GIST仍未被识别，因为KIT蛋白表达并不总是明显的。本研究的目的是识别用于GIST鉴别诊断的新标志物。
通过分析肉瘤转录谱的公开可用数据，我们发现蛋白激酶Cθ（PKC-θ），一种参与T细胞活化的新型PKC亚型，在GIST中高度特异性表达。通过逆转录PCR和蛋白质印迹法证实了PKC-θ在GIST中的表达。通过免疫组织化学对26例GIST、12例非GIST软组织肉瘤和35例其他组织学肿瘤进行了PKC-θ分析。
我们发现所有GIST均表达PKC-θ，而在其他间充质或上皮肿瘤中，包括非GIST KIT阳性肿瘤中未检测到该蛋白。在Cajal间质细胞中也观察到PKC-θ免疫反应性。
我们的结果表明，PKC-θ在GIST标本中通过免疫组织化学很容易检测到，并且它可能是诊断这种恶性肿瘤的敏感和特异性标志物。
