Nielsen Torsten O, Hsu Forrest D, O'Connell John X, Gilks C Blake, Sorensen Poul H B, Linn Sabine, West Robert B, Liu Chih Long, Botstein David, Brown Patrick O, van de Rijn Matt
Department of Pathology and Genetic Pathology Evaluation Centre, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Am J Pathol. 2003 Oct;163(4):1449-56. doi: 10.1016/S0002-9440(10)63502-X.
Histological diagnosis of synovial sarcoma can be difficult. Genome-wide expression profiling has identified a number of genes expressed at higher levels in synovial sarcoma than in other soft tissue tumors, representing excellent candidates for diagnostic immunohistochemical markers. A tissue microarray comprising 77 sarcomas, including 46 synovial sarcomas, was constructed to validate identified markers and investigate their expression in tumors in the differential diagnosis of synovial sarcoma. Immunostaining was performed for two such markers, epidermal growth factor receptor and SAL (drosophila)-like 2 (SALL2), and for fifteen established markers used in the differential diagnosis of sarcomas. As predicted by expression profiling, epidermal growth factor receptor (a potential therapeutic target) and SALL2 stained most cases of synovial sarcoma; staining was significantly less common among other tested sarcomas. Hierarchical clustering analysis applied to immunostaining results for all 18 antibodies showed that synovial sarcomas, leiomyosarcomas, hemangiopericytomas, and solitary fibrous tumors cluster distinctly, and assigned one case with indeterminate histology as a Ewing sarcoma. Digital images from over 2500 immunostained cores analyzed in this study were captured and are made accessible through the accompanying website: http://microarray-pubs.stanford.edu/tma_portal/synsarc.
滑膜肉瘤的组织学诊断可能具有挑战性。全基因组表达谱分析已鉴定出一些在滑膜肉瘤中表达水平高于其他软组织肿瘤的基因，这些基因是诊断性免疫组化标志物的极佳候选者。构建了一个包含77个肉瘤（包括46个滑膜肉瘤）的组织微阵列，以验证已鉴定的标志物，并研究它们在滑膜肉瘤鉴别诊断中的肿瘤表达情况。对两种这样的标志物（表皮生长因子受体和果蝇样2（SALL2））以及用于肉瘤鉴别诊断的15种既定标志物进行了免疫染色。正如表达谱分析所预测的，表皮生长因子受体（一种潜在的治疗靶点）和SALL2在大多数滑膜肉瘤病例中呈阳性染色；在其他测试的肉瘤中，染色明显较少见。对所有18种抗体的免疫染色结果进行的层次聚类分析表明，滑膜肉瘤、平滑肌肉瘤、血管外皮细胞瘤和孤立性纤维性肿瘤明显聚类，并将一例组织学不确定的病例归类为尤因肉瘤。本研究中分析的2500多个免疫染色芯块的数字图像已被捕获，并可通过随附网站获取：http://microarray-pubs.stanford.edu/tma_portal/synsarc 。
