Immunohistochemical evaluation of chemically induced rhabdomyosarcomas in rats: diagnostic utility of MyoD1.
Monoclonal antibodies (mAbs) to selected muscle proteins were assessed as potential immunohistochemical markers to assist in the definitive diagnosis of poorly differentiated soft tissue sarcomas in rats. A series of 7 rat rhabdomyosarcomas (RMS) induced with nickel subsulfide were studied by light microscopy and were evaluated for immunoreactivity to desmin, vimentin, fast (type II isoform) skeletal myosin, alpha-actin (smooth muscle isoform), or MyoD1 (myogenic regulatory protein) mAbs using an avidin-biotin-chromogen technique. Consecutive RMS slices were fixed in 10% neutral buffered formalin (the fixative routinely used in carcinogenicity bioassays) for periods of 3 days or 2 mo prior to paraffin embedding to determine the effect of fixation time on immunoreactivity. Desmin and vimentin mAbs bound to many cells of all tumors, but fixation for 2 mo resulted in irretrievable loss of desmin and vimentin binding. Fast myosin and alpha-actin mAbs bound to many cells in 1 RMS but to < 1% of the cells in the remainder. MyoD1 mAb bound to tumor cell nuclei in 5/7 RMS with no loss of staining in tissue fixed for 2 mo. Results indicate that MyoD1 immunostaining, in contrast to desmin, maintains its sensitivity following prolonged formalin fixation and may be of value to distinguish RMS from other soft tissue sarcomas in the rat.
Newsholme
S J
SJ
Department of Toxicology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. Stephen_J_Newsholme@sbphrd.com
Zimmerman
D M
DM
D000818:Animals; D014408:Biomarkers, Tumor; D002273:Carcinogens / Q000633:toxicity*; D003893:Desmin / Q000032:analysis; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D019042:Muscle Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D017570:MyoD Protein; D009532:Nickel / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012208:Rhabdomyosarcoma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D015534:Trans-Activators
D014408:Biomarkers, Tumor; D002273:Carcinogens; D003893:Desmin; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D015534:Trans-Activators; D009532:Nickel; C017557:nickel subsulfide