The clinical significance of tenascin-C splice variant expression in chondrosarcoma

Objectives: Tenascin-C (TNC) is an oligomeric glycoprotein of the extracell ular matrix that is prominently expressed in malignant tumors. The purpose of this study was: (1) to determine the in vitro TNC splicing pattern in cu ltured human chondrocytes and chondrosarcoma cells, (2) to determine the in vivo TNC splicing pattern in clinical chondrosarcoma specimens, and (3) to perform survival analysis based on the TNC splicing pattern of the tumor s pecimens. Methods: Human articular chondrocytes and chondrosarcoma cells (c ell line JJ012) were grown in a three-dimensional alginate bead system and harvested at two time points. Semiquantitative reverse transcription polyme rase chain reaction (RT-PCR) was used to determine the in vitro TNC splicin g pattern for the two cell types. Clinical chondrosarcoma specimens were ob tained intra-operatively and underwent RT-PCR to determine the in vivo TNC splicing pattern. Specific immunohistochemical staining for the large TNC s plice variant was performed on the clinical specimens. Survival analysis wa s used to determine the association between the specific TNC splicing patte rn and survival. Results: The in vitro mRNA expression pattern of TNC in no rmal human articular chondrocytes was characterized by a high ratio of the small to the large splice variant (TNCsmall:TNClarge), whereas the in vitro mRNA expression pattern for cultured chondrosarcoma cells was characterize d by a low TNCsmall:TNClarge ratio. Clinical chondrosarcoma specimens with a lower TNCsmall:TNClarge ratio showed a trend towards decreased survival. The TNC splicing pattern of these specimens was verified through specific i mmunohistochemical staining for the large TNC isoform. Conclusions: The spe cific TNC splicing pattern may have clinical significance in chondrosarcoma . TNC expression may therefore play a future role in objecitve tumor gradin g and novel therapeutic approaches to this malignancy. Copyright (C) 2001 S . Karger AG, Basel.