Prognostic value of adaptive and innate immune system in soft tissue sarcomas

Abstract

The purpose of this study was to clarify the prognostic significance of the adaptive and innate immune system in soft tissue sarcomas (STS). Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of tumor infiltrating lymphocytes is controversial as the immune system has conflicting roles during cancer development. Tissue microarrays from 249 patients with STS were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the expression of different immune cells.

In univariate analyses, increased numbers of CD20+ lymphocytes in tumor correlated significantly with an improved disease-specific survival (DSS) in patients with wide resection margins (n = 108). In multivariate analyses, a high number of CD20+ lymphocytes in the tumor was an independent positive prognostic factor for DSS in patients with wide resections margins. Co-expression of M-CSF and TGF-beta in tumor and high expression of Ki67 in peritumoral capsule were independent negative prognostic factors for DSS. Increased expression of Skp2 in patients with soft tissue sarcomas is an independent negative prognostic factor for disease-specific survival in women and in patients not administered chemotherapy or radiotherapy.

We found diverse prognostic impacts of expression of Skp2, ER, PGR and DSS in male and female patients with STS. In men, but not women, ER positive / PGR negative co-expression profile was an independent negative prognostic factor for DSS. In women, but not men, high expression of Skp2 was associated with reduced DSS.