Matrix Gene Expression Analysis and Cellular Phenotyping in Chordoma Reveals Focal Differentiation Pattern of Neoplastic Cells Mimicking Nucleus Pulposus Development

• Published in: The American journal of pathology Vol. 158; no. 5; pp. 1571 - 1578
• Main Authors: Gottschalk, Detlev, Fehn, Marita, Patt, Stephan, Saeger, Wolfgang, Kirchner, Thomas, Aigner, Thomas
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.05.2001; ASIP; American Society for Investigative Pathology
• Subjects: Aggrecans; Biological and medical sciences; Cell Differentiation; Chordoma - genetics; Chordoma - metabolism; Chordoma - pathology; Collagen - genetics; Diseases of the osteoarticular system; Extracellular Matrix Proteins - genetics; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Intervertebral Disc - embryology; Intervertebral Disc - pathology; Keratins - analysis; Lectins, C-Type; Lumbar Vertebrae - chemistry; Lumbar Vertebrae - embryology; Lumbar Vertebrae - pathology; Medical sciences; Mucin-1 - analysis; Phenotype; Proteoglycans - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; S100 Proteins - analysis; Short Communications; Tumors of striated muscle and skeleton; Vimentin - analysis; Human; Immunohistochemistry; Chondrocyte; In situ; Diseases of the osteoarticular system; Histiogenesis; Malignant tumor; Hybridization; Nucleus pulposus; Cell differentiation; Pathology; Chordoma; Extracellular matrix; Bone; Molecular biology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64111-9

Chordoma is the fourth most common malignant primary neoplasm of the skeleton and almost the only one showing a real epithelial phenotype. Besides classic chordoma, so-called chondroid chordoma was described as a specific entity showing cartilage-like tissue within chordomatoid structures. However, since its first description, strongly conflicting results have been reported about the existence of chondroid chordoma and several studies suggested chondroid chordomas being in fact low-grade conventional chondrosarcomas. In the present study, we used cytoprotein expression profiling and molecular in situ localization techniques of marker gene products indicative of developmental phenotypes of chondrocytes to elucidate origin and biology of chondroid chordoma. We were able to demonstrate the chondrogenic potential of chordomas irrespectively of the appearance of overt cartilage formation by identifying the multifocal expression of type II collagen, the main marker of chondrocytic differentiation. Additionally, the cartilage-typical large aggregating proteoglycan aggrecan was present throughout all chordomas and, thus, a very characteristic gene product and marker of these neoplasms. Biochemical matrix composition and cell differentiation pattern analysis showed a high resemblance of classic chordomas and in chordoid areas of chondroid chordomas to the fetal chorda dorsalis, whereas chondroid areas of chondroid chordomas showed features similar to adult nucleus pulposus. This demonstrates on the cell function level the chondrocytic differentiation potential of neoplastic chordoid cells as a characteristic facet of chordomas, mimicking fetal vertebral development, ie, the transition of the chorda dorsalis to the nucleus pulposus. Our study firmly establishes a focal real chondrocytic phenotype of neoplastic cells in chordomas. Chondroid chordoma is neither a low-grade chondrosarcoma nor a misnomer as discussed previously.