Wang H, Rodgers W H, Chmell M J, Svitek C, Schwartz H S
Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2550, USA.
J Orthop Res. 1995 Sep;13(5):671-8. doi: 10.1002/jor.1100130506.
Fifteen archival human osteosarcoma specimens were examined by in situ hybridization for the expression of human and mouse transforming growth factor-beta (isoforms 1, 2, and 3), c-fos, and metalloproteinase (stromelysin-3 and matrilysin). Osteosarcoma subtypes were confirmed by review of patients' radiographs, histopathology, and age at diagnosis. The outcome and method of treatment were documented. The subtypes of osteosarcoma consisted of nine conventional osteosarcomas and two each of fibroblastic, telangiectatic, and post-radiation osteosarcomas. Each specimen was histologically examined under light microscopy, and then adjacent paraffin sections were assayed with sense and anti-sense RNA probes by in situ hybridization. The probes localized to the neoplastic cells, confirming the methodology of the technique. Human transforming growth factor-beta 1 had the most uniform binding affinity to the osteosarcomas examined and was more specific in binding than mouse transforming growth factor-beta 1. Specific mRNA encoding for the transforming growth factor-beta s, c-fos, and metalloproteinases are detectable in patterns within osteosarcoma cells, and collectively, their expression parallels the different histopathologic subtypes. The less differentiated subtypes (telangiectatic and post-radiation osteosarcomas) expressed the fewest molecular markers. Osteosarcoma is a heterogeneous tumor. Differential expression of matrilysin in osteosarcoma is the first reported detection of metalloproteinase activity in human skeletal sarcoma.
通过原位杂交技术检测了15份存档的人类骨肉瘤标本，以观察人类和小鼠转化生长因子-β（亚型1、2和3）、c-fos以及金属蛋白酶（基质溶解素-3和基质溶素）的表达情况。通过复查患者的X光片、组织病理学以及诊断时的年龄来确认骨肉瘤的亚型。记录了治疗结果和治疗方法。骨肉瘤亚型包括9例传统骨肉瘤，以及各2例纤维母细胞型、毛细血管扩张型和放疗后骨肉瘤。对每个标本进行组织学检查，然后通过原位杂交技术，使用正义和反义RNA探针检测相邻的石蜡切片。探针定位于肿瘤细胞，证实了该技术的方法学。人类转化生长因子-β1对所检测的骨肉瘤具有最一致的结合亲和力，并且在结合方面比小鼠转化生长因子-β1更具特异性。在骨肉瘤细胞内，可检测到编码转化生长因子-β、c-fos和金属蛋白酶的特定mRNA，总体而言，它们的表达与不同的组织病理学亚型平行。分化程度较低的亚型（毛细血管扩张型和放疗后骨肉瘤）表达的分子标记物最少。骨肉瘤是一种异质性肿瘤。骨肉瘤中基质溶素的差异表达是首次报道在人类骨骼肉瘤中检测到金属蛋白酶活性。
