Low-affinity nerve growth factor receptor (p75) in dermatofibrosarcoma protuberans and other nonneural tumors: A study of 1,150 tumors and fetal and adult normal tissues

Low-affinity nerve growth factor receptor (p75) is a member of the tumor ne crosis factor receptor family. It may modulate the binding of nerve growth factor (NGF) to the functional high-affinity receptor tyrosine kinase (trk) A NGF is thought to be responsible for growth, apoptosis, and function of the nervous system. The presence of this receptor (p75) was determined in a large group of neural and nonneural tumors and fetal and adult tissues. On e thousand one hundred fifty tumors were analyzed with monoclonal antibody for p75, along with selected normal fetal and adult tissues. Immunoreactivi ty for p75 was present in adult pericytes, perivascular fibroblasts, basal cells of several types of epithelia, perineurial cells, and dendritic retic ulum cells. Additionally, a wide zone of subepithelial mesenchyme and skele tal muscle were positive in the first-trimester fetus, but were diminished or negative in the adult. Consistently positive nonneural mesenchymal tumor s included dermatofibrosarcoma protuberans (DFSP), embryonal and alveolar r habdomyosarcoma, synovial sarcoma, and spindle cell hemangio(endotheli)oma. Schwann cell tumors, ganglioneuroma, granular cell tumor, and malignant pe ripheral nerve sheath tumor (MPNST) were also p75 positive. Mesenchymal non neural tumors that were variably positive (32% to 69%) for p75 included fib rosarcoma variants, solitary fibrous tumor, hemangiopericytoma, spindle cel l lipoma, Ewing's sarcoma, mesenchymal chondrosarcoma, and malignant melano ma. Nervous system tumors such as paragangliomas, neuroblastoma, meningioma , and perineurioma and noun ural mesenchymal tumors, including extraskeleta l osteosarcoma, benign fibrous histiocytomas, fibromas, alveolar soft part sarcoma, epithelioid sarcoma, smooth muscle and gastrointestinal stromal tu mors, and angiosarcomas, were almost always negative for p75. Epithelial tu mors that were consistently positive included mixed tumor and adenoid cysti c carcinoma, whereas mesothelioma, adenocarcinomas, and most squamous cell carcinomas were negative. p75 is not a specific marker for nerve sheath tum ors. It is present in a variety of other mesenchymal tumors including synov ial sarcoma and in CD34-positive tumors such as DFSP, spindle cell lipoma, and hemangiopericytoma. The presence of p75 in nonneural tumors such as DFS P and rhabdomyosarcoma mimic its presence in early fetal mesenchyme and ske letal mu cl, suggesting oncofetal expression in these tumors. p75 may be us eful to distinguish DFSP from benign fibrous histiocytoma.This is a US gove rnment work. There are no restrictions on its use.