Magro Gaetano, Salvatorelli Lucia, Vecchio Giada Maria, Musumeci Giuseppe, Rita Alaggio, Parenti Rosalba
Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, Catania, Italy.
Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, Catania, Italy.
Acta Histochem. 2014 Sep;116(7):1134-40. doi: 10.1016/j.acthis.2014.05.010. Epub 2014 Jul 5.
There is increasing evidence that Wilms' tumor transcription factor-1 (WT1) is expressed in the cytoplasm of neoplastic cells from different benign and malignant tumors. Only a few studies on WT1 cytoplasmic immunolocalization are available in pediatric tumors. The aim of the present study was to investigate immunohistochemically the expression and distribution of WT1 in a large series of soft tissue fibroblastic/myofibroblastic lesions occurring in children and adolescents. Notably WT1 was not expressed in nodular fasciitis and desmoid-type (adult) fibromatosis, while it stained diffusely and strongly in several infantile-type fibromatoses, such as fibrous hamartoma of infancy, myofibroma/myofibromatosis, and lipofibromatosis. Interestingly, WT1 cytoplasmic expression was also found in all cases (10/10) of infantile fibrosarcomas examined. The present study shows that a diffuse WT1 cytoplasmic expression is of complementary diagnostic value to conventional myofibroblastic markers (α-smooth muscle actin; desmin) in confirming diagnosis of young-type fibromatoses or infantile fibrosarcoma and in ruling out both desmoid-type fibromatoses and nodular fasciitis. WT1 cytoplasmic expression in infantile fibrosarcoma is a novel finding which could be exploitable as an immunomarker for this tumor. Although highly sensitive, WT1 cytoplasmic immunostaining is not specific for infantile fibrosarcoma, and thus it should be evaluated in the context of a wide immunohistochemical panel when pathologists are dealing with spindle cell lesions of soft tissues in children and adolescents. Accordingly we recommend that a correct diagnosis of fibroblastic/myofibroblastic soft tissue lesion in pediatric patients is usually achieved on the basis of a careful correlation of morphological and immunohistochemical findings in the appropriate clinical context. The different cellular localization of WT1, namely nuclear, cytoplasmic or nucleo-cytoplasmic, in different benign and malignant tumors supports the hypothesis that this transcription factor plays a complex role in tumorigenesis, likely as a chameleon protein functioning as either a tumor suppressor gene or an oncogene, depending on cellular context.
越来越多的证据表明，威尔姆斯瘤转录因子-1（WT1）在来自不同良性和恶性肿瘤的肿瘤细胞胞质中表达。关于WT1胞质免疫定位的研究在儿科肿瘤中仅有少数。本研究的目的是通过免疫组织化学方法研究WT1在一系列发生于儿童和青少年的软组织成纤维细胞/肌成纤维细胞病变中的表达和分布。值得注意的是，WT1在结节性筋膜炎和硬纤维瘤型（成人）纤维瘤病中不表达，而在几种婴儿型纤维瘤病中呈弥漫性强染色，如婴儿纤维性错构瘤、肌纤维瘤/肌纤维瘤病和脂肪纤维瘤病。有趣的是，在所检查的所有婴儿纤维肉瘤病例（10/10）中也发现了WT1胞质表达。本研究表明，弥漫性WT1胞质表达在确认幼年型纤维瘤病或婴儿纤维肉瘤的诊断以及排除硬纤维瘤型纤维瘤病和结节性筋膜炎方面，对传统的肌成纤维细胞标志物（α-平滑肌肌动蛋白；结蛋白）具有补充诊断价值。婴儿纤维肉瘤中WT1胞质表达是一个新发现，可作为该肿瘤的免疫标志物。尽管WT1胞质免疫染色高度敏感，但对婴儿纤维肉瘤并不特异，因此当病理学家处理儿童和青少年软组织的梭形细胞病变时，应在广泛的免疫组织化学检测组合背景下进行评估。因此，我们建议在适当的临床背景下，通过仔细关联形态学和免疫组织化学结果，通常可以对儿科患者的成纤维细胞/肌成纤维细胞软组织病变做出正确诊断。WT1在不同良性和恶性肿瘤中的不同细胞定位，即细胞核、细胞质或核质定位，支持了这一转录因子在肿瘤发生中起复杂作用这一假说——它可能像一种变色龙蛋白，根据细胞环境发挥肿瘤抑制基因或癌基因的作用。
