RETINOBLASTOMA (RB) GENE-PRODUCT EXPRESSION IN LYMPHOMAS - CORRELATION WITH KI67 GROWTH FRACTION

The retinoblastoma susceptibility gene (Rb) has been characterized as a tumour suppressor gene. Rb protein is involved in cell-cycle control , regulating gene transcription. The absence of Rb protein in inherite d retinoblastoma has been proved to be the result of inactivation of b oth Rb alleles through mutation or deletion, according to the general model for suppressor genes. The frequent detection of Rb gene alterati ons in human tumours (retinoblastoma, osteosarcoma, bladder carcinoma, small-cell lung carcinoma) and the correlation with clinical outcome found in some tumours prompted us to study Rb gene expression in lymph oid tumours in an attempt to determine whether Rb gene expression is r elated to histological type and degree of aggressivity in human lympho mas. To establish normal levels of Rb protein, its expression was anal ysed in vitro on cytospin preparations from normal and pokeweed mitoge n (PWM) or phytohaemagglutinin (PHA)-stimulated peripheral blood lymph ocytes (PBLs), using a monoclonal antibody (PMG3-245). Rb protein expr ession in vivo was quantified using a computer analysis system (CAS) o n frozen sections from reactive and neoplastic lymphoid tissue. As a c ontrol of tissue preservation, and to compare Rb expression and growth fraction, the tumours and cells were labelled simultaneously with the Ki67 monoclonal antibody. Normal and stimulated lymphocytes showed a gradual increase of Rb protein during progression of the cell cycle, w ith a peak in the M phase, G0-G1 cells had no detectable levels of Rb protein, suggesting that the Rb gene may act as a 'status quo' cellula r growth fraction control mechanism. In reactive lymphoid tissue, Rb p rotein was mainly expressed in germinal centres (lymph nodes, tonsils) and cortical thymocytes. There was a statistically significant cor-re lation between Ki67 and Rb expression in non-Hodgkin's lymphomas (NHLs ), most low-grade lymphomas having very weak or undetectable levels of Rb protein. The majority of high-grade lymphomas have higher Rb prote in levels. However, a group of ten lymphomas with no Rb protein was fo und, in spite of a Ki67 range similar to that found in the Rb-positive lymphomas. This lack of Rb expression in a subset of high-grade NHLs suggests that Rb deregulation, through deletion, mutation, or lack of transcription, may play a role in this group of tumours. Further studi es should focus on Rb genetic alterations.