Protein Kinase C-theta Expression in Ewing Sarcoma/Primitive Neuroectodermal Tumor and Malignant Peripheral Nerve Sheath Tumor
GH Kang, KM Kim, DY Kang, CK Park. Samsung Medical Center, Seoul, Korea; Chungnam National University, Daejeon, Korea
Background: Systemic treatment options for advanced sarcomas remain limited. No new effective drugs have been recently described and proposed for sarcomas and, therefore, innovative treatment modalities are very welcome and needed. Recently, it has been reported that protein kinase C (PKC)-theta can serve as a novel therapeutic target in gastrointestinal stromal tumor. PKC-theta is involved in neuronal differentiation and is expressed in the nervous system.
Design: To explore PKC-theta expression in Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) and malignant peripheral nerve sheath tumor (MPNST), 21 ES/PNETs and 19 MPNSTs having typical histopathologic and immunohistochemical findings were retrieved from surgical pathology files from Jan 2000 to July 2008. Formalin-fixed, paraffin-embedded tissue was used for PKC-theta immunostaining (clone 27, BD Transduction Laboratories, 1:100). The expression was considered as positive when at least 10% of the tumor cells were stained. The intensity was graded as negative, weak, moderate or strong.
Results: PKC-theta was positive in the cytoplasm of tumor cells. The staining pattern was predominantly diffuse, and dot-like staining was observed in 2 ES/PNET cases. Seven out of 21 (33.3%) cases of ES/PNETs and 17/19 (89.5%) MPNSTs were positive for PKC-theta. In ES/PNETs, the staining intensity was strong and moderate in 1 each case and weak in 5 cases. In MPNSTs, the staining intensity was strong in 4, moderate in 6, and weak in 7 cases.
Conclusions: We first identified PKC-theta expression in ES/PNETs and MPNSTs with a high frequency and strong intensity. Characteristic dot-like staining pattern observed in ES/PNET can also serve as a diagnostic utility. Although biological function of PKC-theta in ES/PNET and MPNST has yet to be explored, our novel findings highlight that PKC-theta warrants clinical evaluation as a potential therapeutic target in those highly aggressive soft tissue sarcomas.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 7, Monday Afternoon