Matrix gene expression analysis and cellular phenotyping in chordoma reveals focal differentiation pattern of neoplastic cells mimicking nucleus pulposus development

Chordoma is the fourth most common malignant primary neoplasm of the skelet on and almost the only one showing a real epithelial phenotype, Besides cla ssic chordoma, so-called chondroid chordoma was described as a specific ent ity showing cartilage-like tissue within chordomatoid structures. However, since its first description, strongly conflicting results have been reporte d about the existence of chondroid chordoma and several studies suggested c hondroid 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 devel opmental phenotypes of chondrocytes to elucidate origin and biology of chon droid chordoma, We were able to demonstrate the chondrogenic potential of c hordomas irrespectively of the appearance of overt cartilage formation by i dentifying the multifocal expression of type II collagen, the main marker o f chondrocytic differentiation. Additionally, the cartilage-typical large a ggregating proteoglycan aggrecan Fc-as present throughout all chordomas and , thus, a very characteristic gene product and marker of these neoplasms. B iochemical matrix composition and cell differentiation pattern analysis sho wed a high resemblance of classic chordomas and in chordoid areas of chondr oid chordomas to the fetal chorda dorsalis, whereas chondroid areas of chon droid chordomas showed features similar to adult nucleus pulposus, This dem onstrates on the cell function level the chondrocytic differentiation poten tial of neoplastic chordoid cells as a characteristic facet of chordomas, m imicking fetal vertebral development, ie, the transition of the chorda dors alis to the nucleus pulposus, Our study firmly establishes a focal real cho ndrocytic phenotype of neoplastic cells in chordomas, Chondroid chordoma is neither a low-grade chondrosarcoma nor a misnomer as discussed previously.