BIOLOGIC AND CLINICAL-SIGNIFICANCE OF CYTOGENETIC AND MOLECULAR CYTOGENETIC ABNORMALITIES IN BENIGN AND MALIGNANT CARTILAGINOUS LESIONS

Cartilaginous neoplasms are often histologically and therapeutically c hallenging. Predicting biologic behavior can be difficult. In this stu dy, 120 nonneoplastic, benign, and malignant cartilaginous lesions fro m 103 patients were cytogenetically analyzed in a 6-year period after short-term culture. For selected cases, fluorescent in situ hybridizat ion (FISH) techniques using chromosome-specific probes were performed on metaphase/interphase preparations and on paraffin-embedded tissue s ections. Clonal abnormalities of chromosomes 2, 3, 5, 7, 8, and 112 we re most frequently observed. Involvement of chromosomes 5, 8, and 12 m ay be etiologically significant because of the gene localizations for the human cartilage link protein, Langer-Giedion syndrome (a rare synd rome characterized by multiple exostoses), and type II collagen (a maj or component of normal cartilage) respectively, to these three chromos omes. That chromosome 7 abnormalities were observed only in malignant tumors is of diagnostic value. The identity of three marker chromosome s and the significance of trisomy 7 (a finding of controversial meanin g), were determined with FISH. That the presence of chromosome aberrat ions and increasing histologic grade strongly correlated (p = 0.001) i s of prognostic importance. Moreover, complex aberrations were observe d nearly exclusively in high-grade tumors (p = 0.001). The data show t hat nonrandom chromosome loci are aberrantly affected in cartilaginous lesions and that these abnormalities may be of significant histopatho genetic consequence. In addition, these chromosome abnormalities appea r to be diagnostically and prognostically valuable in classifying and grading chondromatous neoplasms.