PHENOTYPIC DIVERSITY OF NEOPLASTIC CHONDROCYTES AND EXTRACELLULAR-MATRIX GENE-EXPRESSION IN CARTILAGINOUS NEOPLASMS

Chondrocyte differentiation is characterized by distinct cellular phen otypes, which can be identified by specific extracellular matrix gene expression profiles By applying in situ analysis on the mRNA and prote in level in a series of benign and malignant human chondrogenic neopla sms, we were able to identify for the first time different phenotypes of neoplastic chondrocytes in viva, 1) mature chondrocytes, tc'hich sy nthesized the characteristic cartilaginous extracellular tumor matrix, 2) cells resembling hypertrophic chondrocytes of the fetal growth pla te, 3) cells resembling so-called dedifferentiated chondrocytes, and 4 ) well differentiated chondrocytic cells, which expressed type I colla gen, indicating the presence of post-hypertrophic differentiated neopl astic chondrocytes. Chondrocytes exhibiting a range of phenotypes were found to be present in the same neoplasm. The different observed phen otypes, including the dedifferentiated phenotype, were in contrast to the anaplastic cells of high-grade chondrosarcomas Comparison of expre ssion data with tumor morphology revealed a relationship between the c ellular phenotypes the tumor matrix composition, and the matrix and ce ll molphology within the neoplasms. The distinctly different phenotype s of neoplastic chondrocytes are the basis of the characteristic high biochemical and morphological heterogeneity of chondroid neoplasms and shed light on their biological and clinical behavior.