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A pleiomorphic GH pituitary adenoma from a Carney complex patient displays universal allelic loss at the protein kinase A regulatory subunit 1A (PRKARIA) locus
  1. I Bossis1,
  2. A Voutetakis1,3,
  3. L Matyakhina1,
  4. S Pack1,
  5. M Abu-Asab2,
  6. I Bourdeau1,
  7. K J Griffin1,
  8. N Courcoutsakis1,
  9. S Stergiopoulos1,
  10. D Batista1,
  11. M Tsokos2,
  12. C A Stratakis1
  1. 1Section on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
  2. 2Section of Ultrastructural Pathology, Laboratory of Pathology, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA
  3. 3Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH), Bethesda, MD 20872, USA
  1. Correspondence to:
 Dr C A Stratakis
 Section on Endocrinology and Genetics, DEB, NICHD, NIH, Building 10, Room 10N262, 10 Center Dr. 1862, Bethesda, MD 20892-1862, USA;


Carney complex (CNC) is a familial multiple endocrine neoplasia syndrome associated with GH-producing pituitary tumours and transmitted as an autosomal dominant trait. Mutations of the PRKAR1A gene are responsible for approximately half the known CNC cases but have never found in sporadic pituitary tumours. Pituitary tissue was obtained from an acromegalic CNC patient heterozygote for a common (PRKARIA)i-inactivating mutation. Both immunohistochemistry and electron microscopy showed a highly pleiomorphic pituitary adenoma. The cell culture population appeared morphologically heterogeneous and remained so after more than 30 passages. The mixture was comprised of cells strongly immunostained for GH, spindle-shaped myofibroblast-like cells, and cuboid cells with large axonal projections (negative for GH). The population appeared to have both epithelial and mesenchymal cells. Both at baseline and at passage 30, cytogenetic analysis indicated the presence of normal 46, XY diploid karyotype, whereas losses of the PRKARIAi locus were demonstrated in more than 98% of the cells by fluorescent in situ hybridisation, supporting this gene’s involvement in pituitary tumorigenesis. Allelic loss may have occurred in a single precursor cell type that differentiated and clonally expanded into several phenotypes. Epithelial-to-mesenchymal transition may also occur in CNC-associated pleiomorphic pituitary adenomas.

  • BAC, bacterial artificial chromosome
  • CNC, Carney complex
  • EM, electron microscopy
  • EMT, epithelial-mesenchymal transition
  • FISH, fluorescence in situ hybridisation
  • FSH, follicular stimulating hormone
  • GH, growth hormone
  • LH, luteinising hormone
  • LOH, loss of heterozygosity
  • MAS, McCune-Albright syndrome
  • MEN 1, multiple endocrine neoplasia type 1
  • PKA, protein kinase A
  • PRKAR1A, protein kinase A regulatory subunit type 1A
  • PRL, prolactin
  • TSH, thyroid stimulating hormone
  • TSS, transsphenoidal surgery
  • acromegaly
  • Carney complex
  • growth hormone
  • multiple endocrine neoplasia
  • pituitary tumours

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  • Conflict of interest: none declared.