title: Squamous cell carcinoma-related oncogene is highly expressed in developing, normal, and adenomatous adrenal tissue but not in aggressive adrenocortical carcinomas.
abstract: BACKGROUND
  Our previous work has demonstrated squamous cell carcinoma-related oncogene (SCCRO) expression in adult murine adrenocortical tissue. The aim of this study was to assess patterns of SCCRO expression in the embryonic murine adrenal gland, and in normal and neoplastic human adrenocortical tissues in order to determine its role as a marker of differentiation in adrenocortical development and neoplastic progression.
  
  
  METHODS
  Murine embryos were procured at developmental stages E8 to E18. A tissue microarray was constructed containing 38 normal, 39 adenomatous, and 87 carcinomatous human adrenocortical specimens. Immunohistochemistry for SCCRO was performed and its expression was graded in suitable tissues.
  
  
  RESULTS
  SCCRO expression was detected in the murine adrenal cortex as early as E15 and persisted into the postnatal period. High-level SCCRO expression was identified in 94% of normal (32/34) and adenomatous (29/31) adrenocortical specimens but in only 63% (45/72) of adrenocortical carcinoma (ACC) specimens ( P = .001). Loss of SCCRO expression in primary ACC (13/34 (34%)) correlated with advanced stage ( P = .06), presence of M1 disease at presentation ( P = .03), and worse overall survival ( P = .006).
  
  
  CONCLUSIONS
  SCCRO appears to be a marker of adrenocortical differentiation in both murine and human systems. SCCRO expression may be useful in distinguishing adrenocortical adenomas from ACC. Moreover, loss of SCCRO expression in primary ACC is associated with worse outcome and may be a marker of progressive dedifferentiation in these tumors.
authors.affiliation: Laboratory of Epithelial Cancer Biology, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Sarkaria
authors.forename: Alexander
authors.initials: A
authors.lastname: Stojadinovic
authors.forename: Simon G
authors.initials: SG
authors.lastname: Talbot
authors.forename: Axel
authors.initials: A
authors.lastname: Hoos
authors.forename: Maria E
authors.initials: ME
authors.lastname: Dudas
authors.forename: Murray F
authors.initials: MF
authors.lastname: Brennan
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Ghossein
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D000311:Adrenal Glands / Q000196:embryology* / Q000502:physiology; D018246:Adrenocortical Adenoma / Q000235:genetics*; D018268:Adrenocortical Carcinoma / Q000235:genetics*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D009857:Oncogenes / Q000235:genetics*; D011379:Prognosis; D015843:Serpins / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D015843:Serpins; C051072:squamous cell carcinoma-related antigen