Department of Clinical Pathology, University Hospital of Northern Norway, 9038 Tromsø, Norway.
Int J Oncol. 2011 Apr;38(4):1031-40. doi: 10.3892/ijo.2011.920. Epub 2011 Jan 24.
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.
雌激素(ER)和孕激素受体(PgR)通过配体依赖性和配体非依赖性激活来调节生长和细胞分化。在乳腺癌和妇科肿瘤中,它们的表达是内分泌治疗益处和有利的无治疗预后的已知预测因子。在软组织肉瘤中,其表达谱定义不佳,其意义不确定。我们研究了 ER 和 PgR 在非胃肠道间质瘤软组织肉瘤(非 GIST STS)中的预后影响。收集了 249 例非 GIST STS 患者的肿瘤样本和临床资料,并为每个标本构建了组织微阵列(TMA)。免疫组织化学(IHC)用于评估肿瘤细胞中标志物的表达。在单因素分析中,ER 和 PgR 的表达(分别为 P=0.333 和 0.067)在总队列中均不是显著的预后指标。然而,分别按性别测量时,ER 阳性是女性疾病特异性生存(DSS)的显著有利指标(P=0.017),而 PgR 阳性在男性中具有相反的影响(P=0.001)。在四种可能的共表达谱中,ER-/PgR+在单因素分析中对生存的影响最不利(P<0.001)。在多因素分析中,除了患者国籍、肿瘤深度、组织实体、恶性程度、诊断时转移、手术和阳性切缘外,ER-/PgR+表型还是 DSS 的独立负预后因素(HR=1.9,95%CI=1.2-3.1,P=0.008)。本研究结果表明,ER 和 PgR 在非 GIST STS 中对 DSS 有显著的性别依赖性影响。