Prognostic impact of CD57, CD68, M-CSF, CSF-1R, Ki67 and TGF-beta in soft tissue sarcomas

BACKGROUND Prognostic markers in curable STS may have the potential to guide therapy after surgical resection. The purpose of this study was to clarify the prognostic impact of the presence of cells and growth factors belonging to the innate immune system in soft tissue sarcomas (STS). The significance of macrophages (CD68), their growth factor macrophage colony-stimulating factor (M-CSF), its receptor colony-stimulating factor-1 receptor (CSF-1R), natural killer cells (CD57) and the general immunomodulating molecule (TGF-beta) are all controversial in STS. Herein, these markers are evaluated and compared to the cell proliferation marker Ki67. METHODS Tissue microarrays from 249 patients with non-gastrointestinal (non-GIST) STS were constructed from duplicate cores of viable and representative neoplastic tumor areas and duplicate cores of peritumoral capsule. Immunohistochemistry was used to evaluate the expression of CD68, M-CSF, CSF-1R, CD57, TGF-beta and Ki67 in tumor and peritumoral capsule. RESULTS In univariate analyses increased expression of M-CSF (P = 0.034), Ki67 (P < 0.001) and TGF-beta (P = 0.003) in tumor correlated with shorter disease-specific survival (DSS). Increased expression of CD68 in tumor correlated significantly with malignancy grade (P = 0.016), but not DSS (P = 0.270). Increased expression of Ki67 in peritumoral capsule tended to correlate with a shorter DSS (P = 0.057). In multivariate analyses, co-expression of M-CSF and TGF-beta (P = 0.022) in tumor and high expression of Ki67 (P = 0.019) in peritumoral capsule were independent negative prognostic factors for DSS. CONCLUSIONS Increased co-expression of M-CSF and TGF-beta in tumor in patients with STS, and increased expression of Ki67 in peritumoral capsule were independent negative prognostic factors for DSS.