Posters— Diagnostic Imaging/Pathology

MATRIX GENE EXPRESSION AND CELLULAR PHENOTYPING IN CHONDROID CHORDOMA RE-VEALS FOCAL MATURATION OF NEOPLASTIC CHORDOID CELLS MIMICKING HISTOGENESIS OF DEVELOPING NUCLEUS PULPOSUS

Gottschalk D, Fehn M, Patt S, Saeger W, Kirchner T, Aigner T (Institute of Pathology, FAU Erlangen-Nürnberg, Germany)

Introduction: Beside conventional chordoma (cchor), so called chondroid chordoma (chon chor) is descri-bed as a specific subtype. However, since its first description conflicting results have been reported on the existence of this cartilaginous tumor variant and several studies suggested chon chor being in fact low grade chondrosarcomas. In the present study, we used molecularbiological in-situ localization techniques for mRNAs of different collagen types and the proteins as marker gene products, indicating different phe-notypic or developmental stages of chondrocytes, to elucidate further the origin and histogenesis of the chondroid tumor compartment in chon chor.

Materials & Methods: 7 specimen of chon chor and 14 of cchor were routinely fixed immediately after removal and embedded in paraffin. Additionally, four samples of fetal vertebral columns with remnants of chorda dorsalis (cd) tissue were included. Histomorphological evaluation was performed with HE, GAG’s were visualized by toluidine blue, the presence of collagens by Masson-Goldner’s staining.

Immunohistochernistry: deparaffinized sections were enzymatically pretreated and stained with primary antibodies against collagen type I,II,III,VI and X, aggrecan proteoglycan, S-100, vimentin, EMA,CK-19 and Pan-CK. In-situ hybridisation was performed as described by our group else-where.

Results: We could clearly demonstrate the multifocal deposition of the cartilage-specific type II-coll-agen protein and mRNA in c- and chon chor and thus clearly demonstrate the chondrogenic potential of all chor irrespective the appearance of ouvert cartilage formation. Aggrecan expression was present through-out all chor and, thus, a very characteristic gene product of these neoplasms also in the absence of chon-droid differentiation. There was a clear biochemical resemblance of cchor and the chordoid tumor compart-ment of chon chor to the cd. Respectively, the chondroid tumor compartment of chon chor resembled the adult, matured nucleus pulposus (np). Noteworthy, no type X collagen could be demonstrated in any of our chor, explaining the lack of chondroid calcification in these neoplasms. Further studies have to show if type X-collagen could be used as a marker gene product to differentiate between cartilaginous entities.

Discussion: In the present study, we investigated the biochemical composition of the extracellular tumor matrix as well as the matrix gene expression pattern in conventional and chondroid chordomas in compa-rison to cell and tissue morphology as well as the cytoprotein profile of the neoplastic cells. Herein, the analysis of the matrix gene expression pattern allows to identify and characterize cartilaginous cell differ-entiation within the neoplasms, which is not unequivocally possible by histomorphological, ultrastructural or cytoprotein analysis. Using this approach, we could identify and trace the cellular differentiation pattern in chordomas including the chondroid variants and could identify chondroid differentiation sui generis as a characteristic facette of a subset of chordomas, here mimicking the histogenesis of the developing np.