Estrogen (ER) and progesterone receptor (PgR) regulate growth and cell differentiation upon ligand-dependent and ligand-independent activation. In breast cancer and gynecological tumors their expression are known predictors of endocrine therapy benefits and a favourable therapy-independent prognosis. In soft tissue sarcomas, their expression profile is poorly defined and their significance is uncertain. We investigated the prognostic impact of ER and PgR in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STSs). Tumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays (TMAs) were constructed for each specimen. Immunohistochemistry (IHC) was used to evaluate marker expression in tumor cells. In univariate analyses, the expression of neither ER nor PgR (P=0.333 and 0.067, respectively) were significant prognosticators in the total cohort. However, measured separately for each gender, ER positivity was a significant favourable indicator for disease specific survival (DSS) in women (P=0.017) while PgR positivity had inverse impact in men (P=0.001). Among the four possible coexpression profiles, ER-/PgR+ was significantly least favourable for survival in the univariate analysis (P<0.001). In the multivariate analysis, the ER-/PgR+ phenotype was an independent negative prognostic factor for DSS (HR=1.9, 95% CI=1.2-3.1, P=0.008) in addition to patient's nationality, tumor depth, histological entity, malignancy grade, metastasis at diagnosis, surgery and positive resection margins. The present findings indicate that ER and PgR have significant gender dependent impact on DSS in non-GIST STSs.

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