THE FETAL FORM OF THE ACETYLCHOLINE-RECEPTOR DISTINGUISHES RHABDOMYOSARCOMAS FROM OTHER CHILDHOOD TUMORS

The fetal nicotinic acetylcholine receptor (AChR) of muscle is an olig omeric membrane protein with subunit composition alpha(2) beta delta g amma. After birth, the adult form, in which an E-subunit replaces the gamma-subunit, predominates, and expression of the fetal form is limit ed to thymic myoid cells, extraocular muscles, and denervated striated muscle. We looked for expression of AChR in rhabdomyosarcomas and oth er childhood tumors by reverse transcription polymerase chain reaction and immunohistochemistry. mRNA for the AChR gamma-subunit was detecte d in all embryonal and alveolar rhabdomyosarcomas tested (n = 16) and in some tumors with a rhabdomyomatous component (n = 2) but not in oth er nonrhabdomyomatous tumors of childhood and adults (n = 45). The fet al form of the AChR was detected immunohistochemically in five of eigh t embryonal and four of eight alveolar rhabdomyosarcomas and in two Wi lms' tumors with a rhabdomyomatous component but not in other tumors o r in normal muscle. We conclude that reverse transcription polymerase chain reaction for AChR gamma-subunit could be useful for the diagnosi s of rhabdomyosarcoma of childhood and for the detection of micrometas tases and minimal residual disease. In addition, the fetal AChR protei n is the first extracellular tumor marker that can distinguish rhabdom yosarcomas from nonrhabdomyomatous tumors and from normal muscle. Our findings, therefore, imply that the fetal AChR may be a target for in vivo imaging and, as AChR internalization and degradation is increased by antibody-induced cross-linking, may also provide a sensitive and s pecific target for immunotherapeutic strategies.