title: CRX is a diagnostic marker of retinal and pineal lineage tumors.
abstract: BACKGROUND
  CRX is a homeobox transcription factor whose expression and function is critical to maintain retinal and pineal lineage cells and their progenitors. To determine the biologic and diagnostic potential of CRX in human tumors of the retina and pineal, we examined its expression in multiple settings.
  
  
  RESULTS
  Using situ hybridization and immunohistochemistry we show that Crx RNA and protein expression are exquisitely lineage restricted to retinal and pineal cells during normal mouse and human development. Gene expression profiling analysis of a wide range of human cancers and cancer cell lines also supports that CRX RNA is highly lineage restricted in cancer. Immunohistochemical analysis of 22 retinoblastomas and 13 pineal parenchymal tumors demonstrated strong expression of CRX in over 95% of these tumors. Importantly, CRX was not detected in the majority of tumors considered in the differential diagnosis of pineal region tumors (n = 78). The notable exception was medulloblastoma, 40% of which exhibited CRX expression in a heterogeneous pattern readily distinguished from that seen in retino-pineal tumors.
  
  
  CONCLUSIONS
  These findings describe new potential roles for CRX in human cancers and highlight the general utility of lineage restricted transcription factors in cancer biology. They also identify CRX as a sensitive and specific clinical marker and a potential lineage dependent therapeutic target in retinoblastoma and pineoblastoma.
authors: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors: Sandro
authors: S
authors: Santagata
authors: Cecile L
authors: CL
authors: Maire
authors: Ahmed
authors: A
authors: Idbaih
authors: Lars
authors: L
authors: Geffers
authors: Mick
authors: M
authors: Correll
authors: Kristina
authors: K
authors: Holton
authors: John
authors: J
authors: Quackenbush
authors: Keith L
authors: KL
authors: Ligon
mesh_terms: D000818:Animals; D019070:Cell Lineage; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009369:Neoplasms / Q000378:metabolism*; D010870:Pineal Gland / Q000473:pathology*; D012160:Retina / Q000473:pathology*; D019572:Retinal Neoplasms / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D015534:Trans-Activators; C109288:cone rod homeobox protein