Goldsmith Jeffrey D, Pawel Bruce, Goldblum John R, Pasha Terri L, Roberts Shelley, Nelson Peter, Khurana Jasvir S, Barr Frederic G, Zhang Paul J
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19147, USA.
Am J Surg Pathol. 2002 Dec;26(12):1627-33. doi: 10.1097/00000478-200212000-00011.
Placental alkaline phosphatase (PLAP) is normally produced by primordial germ cells and syncytiotrophoblasts, and the detection of its expression has been useful in the diagnosis of germ cell tumors. We have recently observed PLAP immunoreactivity in normal human adult and fetal muscle tissue. Based on this observation, we explored the possible role of PLAP in the diagnosis of soft tissue tumors. A total of 271 tumors were studied. These included tumors with myogenic, neural, fibrous, myofibroblastic, lipomatous, neuroepithelial, perivascular, and epithelial differentiation. A formalin-fixed, paraffin-embedded section from each tumor was stained with PLAP monoclonal antibody using standard immunohistochemical methods preceded by antigen retrieval. In addition, western blotting with PLAP monoclonal antibodies was performed on fresh samples from a uterine leiomyoma, grossly normal myometrium, and placenta. Also, formalin-fixed sections of fetal skeletal muscle were labeled with double immunohistochemistry techniques using antibodies to myogenin and PLAP. Cytoplasmic PLAP reactivity was detected in all leiomyomas and rhabdomyosarcomas (100%), 7 of 15 (46%) leiomyosarcomas, 15 of 19 (79%) desmoplastic small round cell tumors, 2 of 15 (13%) gastrointestinal stromal tumors, 1 of 8 (13%) Wilms' tumors, 1 of 9 synovial sarcomas (9%), and 2 of 7 (29%) myofibroblastic tumors. No PLAP reactivity was detected in hyperplastic scars, nodular fasciitis, or the other remaining soft tissue and epithelial tumors. Double immunohistochemistry studies showed coexpression of myogenin and PLAP in fetal skeletal muscle cells, and western blot analysis showed a 70-kDa band in samples derived from grossly normal placenta, benign myometrium, and a uterine leiomyoma. PLAP immunoreactivity is detected in soft tissue tumors with known myogenic differentiation. PLAP immunoreactivity seems to relate to the degree of myogenic differentiation in soft tissue tumors and is more frequently expressed in cells with skeletal muscle differentiation and least in those with myofibroblastic features. The biologic function of PLAP in muscle and tumors with myogenic differentiation is unknown and merits further investigation. In addition to its role as a germ cell marker, PLAP may also be used as a myogenic marker in the diagnosis of soft tissue tumors.
胎盘碱性磷酸酶(PLAP)通常由原始生殖细胞和合体滋养层细胞产生,其表达检测在生殖细胞肿瘤的诊断中具有重要作用。我们最近在正常成人及胎儿肌肉组织中观察到了PLAP免疫反应性。基于这一观察结果,我们探讨了PLAP在软组织肿瘤诊断中的可能作用。共研究了271例肿瘤,包括具有肌源性、神经源性、纤维性、肌纤维母细胞性、脂肪性、神经上皮性、血管周围性和上皮性分化的肿瘤。采用标准免疫组织化学方法,在抗原修复后,用PLAP单克隆抗体对每个肿瘤的福尔马林固定、石蜡包埋切片进行染色。此外,用PLAP单克隆抗体对子宫平滑肌瘤、大体正常的子宫肌层和胎盘的新鲜样本进行了蛋白质印迹分析。同时,用抗生肌蛋白和PLAP抗体,通过双重免疫组织化学技术对胎儿骨骼肌的福尔马林固定切片进行标记。在所有平滑肌瘤和横纹肌肉瘤(100%)、15例平滑肌肉瘤中的7例(46%)、19例促纤维组织增生性小圆细胞肿瘤中的15例(79%)、15例胃肠道间质瘤中的2例(13%)、8例肾母细胞瘤中的1例(13%)、9例滑膜肉瘤中的1例(9%)以及7例肌纤维母细胞瘤中的2例(29%)中检测到细胞质PLAP反应性。在增生性瘢痕、结节性筋膜炎或其他剩余的软组织和上皮性肿瘤中未检测到PLAP反应性。双重免疫组织化学研究显示,生肌蛋白和PLAP在胎儿骨骼肌细胞中共表达,蛋白质印迹分析显示,在大体正常胎盘、良性子宫肌层和子宫平滑肌瘤的样本中出现一条70 kDa的条带。在已知具有肌源性分化的软组织肿瘤中检测到PLAP免疫反应性。PLAP免疫反应性似乎与软组织肿瘤的肌源性分化程度有关,在具有骨骼肌分化的细胞中表达更频繁,而在具有肌纤维母细胞特征的细胞中表达最少。PLAP在肌肉和具有肌源性分化肿瘤中的生物学功能尚不清楚,值得进一步研究。除了作为生殖细胞标志物的作用外,PLAP还可作为肌源性标志物用于软组织肿瘤的诊断。