Cell proliferation assessed by KI-67 immunoreactivity on formalin fixed tissues is a predictive factor for survival in prostate cancer

Purpose: Proliferation rate may be an important determinant of tumor progression. To evaluate the predictive value of proliferation, immunoreactivity for the proliferation associated antigen Ki-67 was related to survival in a series of patients with prostate cancer. Materials and Methods: Formalin fixed tissue, obtained by transurethral resection from 125 previously untreated prostate tumors, was examined with an immunohistochemical method for Ki-67. Ki-67 index was defined as the percentage of immunoreactive cells in a tumor. Patients were followed with surveillance after transurethral resection. The cause of death was determined by examination of patient records 11 to 19 years postoperatively (mean followup 71 months). At evaluation 17 patients (14%) were still at risk and 55 (44%) had died of prostate cancer. Results: Mean Ki-67 index was 2.1. Ki-67 index correlated with grade (p < 0.0005) and weakly with stage (p = 0.019). Mean survival of patients with a Ki-67 index of more than 3 was less than half that of patients with a Ki-67 index of less than 3 (53 versus 132 months, p < 0.00005). The difference in survival remained in an analysis of the intermediately differentiated tumors (61 versus 126 months, p = 0.0032). In a Cox multiple regression analysis for cancer specific survival, including Ki-67 index, grade, stage, metastasis and age, Ki-67 index remained an independent predictive factor. Conclusions: Our study indicates that proliferation rate, assessed by Ki-67 immunoreactivity in formalin fixed tissues, is a predictive marker for outcome in prostate cancer.