COLONIC RETINOBLASTOMA PROTEIN AND PROLIFERATION IN CANCER AND NONCANCER PATIENTS

Both suppressor oncogene and proliferative activity are believed to in dicate colon cancer risk. The retinoblastoma Gib) gene is a suppressor oncogene affecting cell differentiation. Retinoblastoma gene inactiva tion is associated with tumour development. However, the relation of t he Rb protein to cell proliferation and colon tumour formation is unkn own. Retinoblastoma protein quantity was correlated with proliferative activity in flat, unaffected mucosa specimens from 36 cancer patients , 21 non-cancer control subjects and in 29 tumour tissue samples from cancer patients. Nuclear Rb protein was measured by using automated CA S-200 image analysis of monoclonal antibody labelled frozen sections f rom fresh, surgically removed tissue. All colon cells within 15 whole crypts were imaged. Proliferative activity was also measured by using image analysis with Ki-67 monoclonal antibody. Retinoblastoma protein content correlated directly with proliferative activity in flat: mucos a of non-cancer control subjects (r=0.63; P <0.001; n=21). A significa nt correlation was also found in flat mucosa specimens of non-metastat ic (Duke's stages A and B) cancer patients (r=0.52; P <0.01; 22). Howe ver, Rb protein did not correlate with proliferation in flat mucosa fr om metastatic (Duke's stages C and D) cancer patients (r=0.03; NS; n=1 4) or in cancer tissue (r=0.068; NS; 29). Mucosal Rb protein in the co lon normally increases as proliferation increases. Dissociation betwee n Rb protein and colon proliferation may occur in flat mucosa in patie nts with a higher risk of metastatic tumour growth. Future studies com paring Rb protein quantity and proliferative activity may help identif y high-risk colon cancer patients.