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Mesenchymal Chondrosarcoma: Molecular Characterization by a Proteomic Approach, with Morphogenic and Therapeutic Implications

Address correspondence to Robert E. Brown, M.D., Division of Laboratory Medicine, Geisinger Medical Center, Danville, PA 17822-0131, USA; tel 570 271 6332; fax 570 271 6105; e-mail rebrown{at}geisinger.edu.

This study characterizes 3 cases of mesenchymal chondrosarcoma (MC) utilizing a proteomic approach that allows for the detection, visual quantification, cellular compartmentalization, and assessment of the functional state of certain proteins that may promote tumor growth and/or oppose apoptosis. Immunohistochemical procedures were performed to detect the following protein antigens: CD99, interleukin (IL)-1, IL-6, transforming growth factor (TGF)-, conventional (c) protein kinase C (cPKC)-, cPKC-ßII, phosphorylated (p)-PKC-/ßII, c-kit (CD117), platelet-derived growth factor receptor (PDGFR)-, PDGFR-ß, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)-2/neu, cathepsin D, angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor, p21ras, the subunit of farnesyl and geranylgeranyl transferase (FT/GGT), phospho (p)-c-Jun N-terminal kinase (p-JNK), p-p38 mitogen-activated protein kinase (MAPK), cyclin D1, c-Jun, Ki-67, bc1-2, TGF-ß1 latency-associated peptide (LAP), TGF-ßRII, and cyclooxygenase (COX)-2. Immunoreactivities were scored from 0 to 3+ positivity using bright-field microscopy. The results showed that malignant mesenchymal chondroblasts exhibit stronger expressions of CD99, IL-1, cPKC-, p-PKC-/ßII, PDGFR-, p-JNK, Ki-67, and bc1-2 antigens than their more mature-appearing chondrocytic counterparts in MC. In conclusion, molecular profiling of mesenchymal chondrosarcoma using a proteomic approach characterized the mesenchymal chondroblasts as possessing pathways that incorporate PKC- and PDGFR- signaling and anti-apoptotic bc1-2 expression. Specific therapies to target the mesenchymal chondroblasts in mesenchymal chondrosarcoma might include interferon-, rapamycin, ciprofloxacin, and STI571.

Keywords: mesenchymal chondrosarcoma, proteomics, neoplasia, apoptosis

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