Röpke 28_4

Loss of function of the human retinoblastoma gene (Rb) is a frequent genetic abnormality in human malignancies and causes a disturbance in the cell cycle and loss of normal proliferation and differentiation. We studied the loss of heterozygosity (LOH) of the Rb gene in 31 formalin-fixed, paraffin-embedded cartilaginous tumors using polymerase chain reaction. The tumors were subdivided into 8 cases of dedifferentiated (DD) chondrosarcoma, 17 cases of conventional chondrosarcoma (nine grade 1, seven grade 2 and one grade 3), 4 enchondromas and 2 chondroblastomas. Both components of DD chondrosarcoma, the low-grade and anaplastic components, were separated by a microdissection approach. The genetic data were correlated with the expression of the Rb protein examined by Rb immunohistochemistry. We found Rb-LOH in one grade 3 chondrosarcoma, and in the anaplastic component in 7 of 8 cases of DD chondrosarcoma (89% of all high-grade chondrosarcomas). All tumors with Rb-LOH were immunohistochemically Rb-negative. The only case of DD chondrosarcoma negative for Rb-LOH in both components of the tumor also showed weak expression of the Rb protein in the anaplastic component. All benign cartilaginous tumors, low-grade chondrosarcomas and lowgrade tumor components of DD chondrosarcomas were negative regarding Rb-LOH but positive in Rb immunohistostaining. We concluded that Rb-LOH predominantly occurs in high-grade chondrosarcomas. However, it is not a marker for identifying low-grade tumors with a tendency towards progression or local recurrence.