Spatial expression of the FGFR2b splice isoform and its prognostic significance in endometrioid endometrial carcinoma

Patient demographic, clinicopathologic and survival outcome data and tissue samples were obtained from women at different menstrual periods with apparent normal endometrium, women with hyperplasia and endometrial cancer. Samples are collected from Mater Hospital (Brisbane, Australia), Tissue microarray samples from US Biomax and 460 samples from Vancouver achieved cohort samples collected for genomic profiling by the Canadian group.

All samples were assessed for Fibroblast Growth Factor Receptor 2 isoforms (FGFR2b and FGFR2c mRNA) using a novel BaseScope RNA in situ hybridisation assay developed by our laboratory. The FGFR2 protein in the samples was assessed using immunohistochemistry. Using the FGFR2b and FGFR2c mRNA pattern of expression, we categorised endometrial cancer into four categories. The FGFR2b and FGFR2c mRNA expression were associated with the clinicopathologic profiles and clinical outcomes. We found exclusive FGFR2b isoform expression on the epithelial compartment of normal endometrium and hyperplasia without atypia and FGFR2b expression was associated with longer progression-free survival and disease-specific survival.

本研究收集了处于不同月经周期、具有正常子宫内膜的妇女、患有子宫内膜增生症及子宫内膜癌的妇女的流行病学、临床病理学及生存结果数据以及组织样本。样本分别来自澳大利亚布里斯班Mater医院、US Biomax组织微阵列样本以及加拿大研究团队收集的用于基因组分析的温哥华队列的460份样本。所有样本均经我们实验室开发的新型BaseScope RNA原位杂交检测方法对成纤维细胞生长因子受体2异构体（FGFR2b和FGFR2c mRNA）进行了评估。样本中的FGFR2蛋白通过免疫组化技术进行了检测。根据FGFR2b和FGFR2c mRNA的表达模式，我们将子宫内膜癌分为四类。FGFR2b和FGFR2c mRNA的表达与临床病理学特征及临床预后相关。我们发现，在正常子宫内膜和增生症的腺上皮部分存在独特的FGFR2b异构体表达，且FGFR2b的表达与更长的无进展生存期和疾病特异性生存期相关。