Wilms tumor transcription factor-1 (WT1) is encoded by Wilms tumor suppressor gene located on chromosome 11p13. Although WT1 was originally identified as a tumour suppressor, there is increasing evidence indicating its role as a potential oncogene involved in proliferation and apoptosis, depending on the cellular context. While it is widely known that many malignant tumors (nephroblastoma, ovarian and mesothelial neoplasms, Sertoli cell tumor and desmoplastic small round cell tumor) exhibit nuclear expression of WT1, many pathologists are not aware of the possibility that this tumor transcription factor may be detected concurrently in the cytoplasm of the above mentioned tumors, or exclusively in the cytoplasm of other tumors, such as vascular neoplasms. Although the cytoplasmic immunohistochemical expression of WT1 was originally interpreted as a cross-reactivity with an epitope unrelated to WT1, accumulating data from in vitro studies and Western blot analyses confirm the specificity of the cytoplasmic staining. In this regard, there is some evidence that WT1 is also expressed in the cytoplasm of human rhabdomyosarcomas suggesting its potential diagnostic use in the context of pediatric small round blue cell tumors. The significance of WT1 expression in rhabdomyosarcoma cells is still to be established. The aim of the present study was to immunohistochemically investigate the expression and distribution of WT1 in developing, adult and neoplastic human skeletal muscle tissues, using antibody clone 6F-H2 directed to the. WT1 N-terminus of the protein. Materials and Methods Tissues samples were collected from: i) 15 human fetuses obtained from legal interruptions, ranging from the 7th to the 24th week of gestational age; ii) 10 samples of adult normal skeletal muscle tissue included in specimens from surgical resection of soft tissue tumors; iii) 2 cases of adult soft tissue rhabdomyomas; iv) 20 cases of pediatric soft tissue rhabdomyosarcomas, including both embryonal and alveolar variants; v) 4 cases of adult soft tissue pleomorphic rhabdomyosarcomas. Results: During all the different phases of development studied, skeletal muscle cells of the trunk, head and neck, and extremities showed a strong and diffuse cytoplasmic expression of WT1. In adults a mosaic pattern of expression, consisting of WT1-negative skeletal muscle cells alternating with a minor number of positive cells was seen. The extent of cytoplasmic staining was extremely variable in the different muscle cells, ranging from focal to diffuse. Notably, WT1 expression was completely lacking in the two cases of soft tissue rhabdomyomas, while it was strongly and diffusely expressed in the cytoplasm of the neoplastic cells of all cases of rhabdomayosarcomas, including embryonal, alveolar and pleomorphic types. No nuclear WT1 staining was obtained in any of the tissues studied. Discussion: The present study shows that WT1 is developmentally expressed in the cytoplasm of human skeletal muscle tissue from the 7th week of gestational age. The comparative evaluation of the immunohistochemical findings in the different tissues reveals that the cytoplasmic expression of WT1 in rhabdomyosarcomas may represent an ontogenetic reversal, and this nuclear transcription factor can also be considered an oncofetal protein.
|Titolo:||A COMPARATIVE IMMUNOHISTOCHEMICAL STUDY OF ONCOFETAL CYTOPLASMIC WT1 EXPRESSION IN HUMAN FETAL, ADULT AND NEOPLASTIC SKELETAL MUSCLE|
|Data di pubblicazione:||2011|
|Appare nelle tipologie:||4.1 Contributo in Atti di convegno|