Prospective evaluation of Ki-67 system in histological grading of soft tissue sarcomas in the Japan Clinical Oncology Group Study JCOG0304

BACKGROUND: The correct clinical staging of soft tissue sarcomas (STS) is critical for the selection of treatments. The staging system consists of histological grade of the tumors and French Federation of Cancer Center (FNCLCC) system based on mitotic count is widely used for the grading. In this study, we compared the validity and usefulness of Ki-67 grading system with FNCLCC system in JCOG0304 trial which investigated the efficacy and safety of perioperative chemotherapy with doxorubicin and ifosfamide for STS. METHODS: All 70 eligible patients with STS in the extremities treated by perioperative chemotherapy in JCOG0304 were analyzed. Univariate and multivariate Cox regression analyses were conducted to investigate an influence on overall survival. RESULTS: The reproducibility of Ki-67 grading system in the histological grading of STS was higher than FNCLCC system (κ = 0.54 [95 % CI 0.39–0.71], and 0.46 [0.32–0.62], respectively). Although FNCLCC grade was not associated with overall survival (OS) in univariate analysis (HR 2.80 [0.74–10.55], p = 0.13), Ki-67 grading system had a tendency to associate with OS in univariate analysis (HR 4.12 [0.89–19.09], p = 0.07) and multivariate analysis with backward elimination (HR 3.51 [0.75–16.36], p = 0.11). CONCLUSIONS: This is the first report demonstrating the efficacy of Ki-67 grading system for the patients with STS in the prospective trial. The results indicate that Ki-67 grading system might be useful for the evaluation of histological grade of STS.