Proliferative activity (Ki-67 expression) and outcome in high grade osteosarcoma: A study of 27 cases

Abstract

Purpose. Although pre-operative chemotherapy has improved the prognosis for individuals with osteosarcoma, approximately 40% of patients will die of their disease. The aim of this study was to quantitate proliferative activity in high grade osteosarcomas and to determine whether proliferation is a prognostic factor. Patients. The study consisted of 27 patients with high grade non-metastatic osteosarcoma at various sites for whom pre-operative biopsies and resection specimens were available for review. All patients were treated similarly and had at least 24 months' follow-up from the date of diagnosis. Methods. Proliferative activity (Ki-67 expression) was examined in the diagnostic biopsies immunohistochemically using the MIB-1 antibody. Proliferation was quantitated in two ways; (1) the number of immunopositive cells was counted manually using an ocular grid; or (2) the percentage of immunopositive nuclear area was assessed using morphometric image analysis. Proliferative index was evaluated in relation to patient outcome. Results. Proliferative activity was seen in all biopsies. The median proliferative index as determined by counting cells was 24% (mean of 27%, range of 7-61%) and by image analysis was 2% (mean 3%, range 0.32-8.4). The correlation between MIB-1 proliferation indices determined either by image analysis methodology or manual cell counting was high (Spearman's rho=0.79). Proliferative index did not appear to predict either disease-free or overall survival. Discussion. Tumor proliferation does not appear to be prognostic for high grade osteosarcomas. Whether assessment of this feature in conjunction with other tumor characteristics might be prognostic requires further study.