1406

CRX

CORD2|CRD|LCA7|OTX3;cone-rod homeobox;CRX;cone-rod homeobox

cone-rod homeobox protein|orthodenticle homeobox 3

19q13.3

protein-coding

tumor-specific immunohistochemical markers are valuable in the differential diagnosis of malignant small round cell tumors (MSRCTs). The cone-rod homeobox-containing gene (CRX) is a transcription factor that is preferentially expressed in retinal photoreceptor cells. It has been shown that the CRX antibody is a good immunohistochemical marker to differentiate retinoblastoma from other intracranial MSRCTs. Outside of the central nervous system, however, the usefulness of CRX immunohistochemistry in establishing a diagnosis of metastaticretinoblastoma is uncertain, as the expression of CRX in primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES), neuroblastoma, and other MSRCTs is unknown. Archival specimens from resections, core biopsies, and bone marrow biopsies of 41 neuroblastomas, 24 PNET/ES, 19 embryonal rhabdomyosarcomas, 17 alveolar rhabdomyosarcomas, 17 Wilms tumors, 14 desmoplastic small round cell tumors, 20 medulloblastomas, 9 pineal tumors, 17 melanocytic tumors (compound and Spitz nevi), and 8 retinoblastomas were immunostained for CRX. ALL retinoblastomas had strong diffuse nuclear immunoreactivity for CRX; 8 of the 20medulloblastomas showed strong nuclear immunoreactivity either in occasional clusters of tumor cells or in rare single scattered tumor cells; 3 of the 9 pineal tumors showed strong nuclear immunoreactivity in approximately 40% to 50%of the tumor cells. Neuroblastomas, PNET/ES, embryonal rhabdomyosarcomas, alveolar rhabdomyosarcomas, Wilms tumors, desmoplastic small round cell tumors, and melanocytic tumors were ALL negative. Scant nonspecific cytoplasmic stainingwas observed in some tumors, mostly PNET/ES. These findings suggest that CRX is a useful marker to discriminate metastatic retinoblastoma from other, more common,MSRCTs of childhood.