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

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Abstract
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. Cancer 2001;92:869–74. © 2001 American Cancer Society.