High Ki-67 proliferative index predicts disease specific survival in patients with high-risk soft tissue sarcomas

BACKGROUND. Soft tissue sarcomas (STSs) are heterogeneous neoplasms that have variable clinical outcome. Several clinical parameters and few molecular markers, including Ki-67 proliferative index, have been shown to correlate with patient prognosis. To the authors' knowledge, no definitive report exists to identify one molecular marker that can be analyzed easily in a clinical setting and that predicts survival in a cohort of patients with high-risk STS of identical clinical characteristics but variable outcome. METHODS. The influence of clinical prognostic factors was eliminated by selecting two patient groups with identical high-risk characteristics: large (> 10 cm), high-grade, deep, completely resected primary extremity STS (n = 47). Patients in the first group remained disease free (no evidence of disease [NED]) after primary tumor treatment (n = 19), whereas patients in the second group subsequently died of disease (DOD; n = 28). Triplicate 0.6-mm core biopsies from defined morphologic areas of paraffin embedded primary tumors were assembled on a tissue microarray and analyzed by immunohistochemistry with the MIB-1 antibody, and Ki-67 proliferative indices were correlated with patient outcome. RESULTS. High Ki-67 proliferative index, defined as greater than 30% tumor cells showing nuclear immunoreactivity, was significantly more frequent in the DOD group than in the NED group and was associated with tumor-related mortality (P = 0.02). This marker identifies an especially aggressive malignant phenotype within a cohort of high-risk tumors that is based on well established clinical and pathologic parameters alone and is easy to use in a clinical setting. CONCLUSIONS. On the basis of these data and previous reports, high Ki-67 proliferative index is suggested as a significant factor for predicting the prognosis of patients with high-risk STS and should be evaluated prospectively based on clinical trials. (C) 2001 American Cancer Society.