We established a murine osteosarcoma cell line (LM8) with high metastatic potential to the lung from murine Dunn osteosarcoma using 8 repeated Fidler's procedures. We performed the biological characterization of the LM8 and the maternal Dunn cell lines in vitro and in vivo. Morphologically, LM8 possesses many fillopodial protrusions, lamellipodial structures surrounding the cell surface and membrane ruffles suggesting enhanced cell motility. The increased matrix metalloproteinase (MMP) 2 activity of this cell line might help cell invasion after penetration of the endothelial (mesothelial) cell layer. This cell line exhibited high in vitro invasive activity when seeded onto the mesothelial cell monolayer. Higher expression of VEGF mRNA in this cell line might facilitate neovascularization at the site of metastaisis, resulting in extremely high metastaic potency after i.v. injection. LM8 also showed a high metastic incidence (7/7) to the lung even after s.c. transplantation into the back space of mice. This cell line can provide an excellent tool for studying inhibitory agents against pulmonary metastasis as well as the various important factors involved in metastasis of osteosarcoma. Int. J. Cancer 76:418–422, 1998.© 1998 Wiley‐Liss, Inc.

Proliferative activity of soft tissue sarcomas (STS) in 34 cases was estimated by immunohistochemical procedures (avidin-biotin complex [ABC] method) with monoclonal antibody Ki-67 which reacts with a nuclear antigen expressed in all phases of cell cycle except G0. In 20 of 34 cases (59%), varying numbers of Ki-67-positive tumor cells were detected with a range from 5 to 382 per 10 high power fields (HPF) (mean 57.2/10 HPF). Ki-67 index (the number of Ki-67-positive tumor cells/10 HPF) positively correlated with mitotic count (r = 0.428, P less than 0.02), cellularity (r = 0.447, P less than 0.01), and histologic grade (r = 0.473, P less than 0.01). The Ki-67 low index group (less than 50/10 HPF) showed more favorable prognosis than the high index group (more than 50/10 HPF) (P less than 0.005). Three cases with low mitotic count and unfavorable prognosis were proved to be the Ki-67 high index group (142-382/10 HPF). These results indicated that reactivity of tumor cells for Ki-67 is a useful prognostic marker in the patients with STS, and might be used as one of the histologic factors for the grading of STS.

The prognostic implication of SYT-SSX fusion type in synovial sarcomas is still controversial. The aim of this study is to clarify the prognostic impact of fusion type, in association with other clinical factors, in patients with synovial sarcoma in Japan. Data on 108 SYT-SSX fusion transcriptpositive patients with synovial sarcoma, treated in 11 tertiary referral cancer centers in Japan, were retrospectively analyzed. The following parameters were examined for their potential prognostic impact: SYT-SSX fusion type, patient age at presentation, sex, primary tumor location, tumor size, histological subtype, histological grade, treatment modalities and disease stage at presentation. Among the patients with localized disease at presentation, 5-year overall survival (OS) for SYT-SSX1 and-2 subgroups were 84.4 and 74.9%, respectively (P=0.244). Five-year metastasis-free survival (MFS) rates were 67.8% for SYT-SSX1 and 68.5% for SYT-SSX2 (P=0.949). Univariate survival analyses for 91 patients with localized disease at presentation showed that tumor size was the only significant prognostic factor for OS (P=0.0033) and MFS (P=0.0029) and the histological grade was marginally significant for MFS (P=0.0785), whereas the SYT-SSX fusion type and other variables were not. Multivariate survival analyses further indicated that tumor size was the most significant independent prognostic factor for OS and MFS and the histological grade was also significant for MFS. In conclusion, the SYT-SSX fusion type is not a significant prognostic factor unlike tumor size, followed by histological grade for patients with localized synovial sarcoma in Japan.

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