title: Crosstalk between tumor blood vessels heterogeneity and hormonal profile of pituitary adenomas: evidence and controversies.
abstract: OBJECTIVE
  Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous clinical behaviour. Angiogenesis and tumor blood vessels' role in pathogenesis, remain one of the great pituitary tumor mysteries. No connection between tumor vessel heterogeneity, hormonal profile and biological behaviour has been reported. We aimed to study pituitary adenomas blood vessels concerning their immature, intermediate or mature phenotype and microvessel density, correlated with immunohistochemical hormonal profile and hormone values in serum and cerebrospinal fluid.
  
  
  METHODS
  We classified pituitary adenomas according to hormone profile and we applied a double immunostaining highlighting both endothelial and perivascular cells for a more accurate assessment of blood vessel types.
  
  
  RESULTS
  Overall microvessel density was found to be highest in growth hormone-secreting adenomas (48.51 ± 12.15) and lowest in prolactinomas (29.15 ± 18.78). When we differentially counted tumor blood vessels we observed a predominance of immature and intermediate blood vessels compared to mature ones. A significant correlation was found between immature tumor blood vessels and tissue prolactin expression, as assessed by immunhistochemistry (p=0.044). A partial correlation was found between serum (p=0.036) and cerebrospinal prolactin values (p=0.006) with immature and intermediate blood vessels. Also, a partial correlation has been reported only between mature blood vessels and cerebrospinal fluid prolactin values (p=0.008). No correlation was obtained for other types of pituitary adenomas.
  
  
  CONCLUSIONS
  Our results suggest a strong involvement of prolactin with a dual role in pituitary adenomas vasculature remodelling by acting both on endothelial and perivascular cells, a finding that could partially explain discrepancies between clinical diagnosis and hormonal profile.
authors.affiliation: Department of Microscopic Morphology/Histology, Angiogenesis Research Center "Victor Babes", University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Bălinişteanu
authors.affiliation: Department of Microscopic Morphology/Histology, Angiogenesis Research Center "Victor Babes", University of Medicine and Pharmacy, Timisoara, Romania ancacimpean1972@yahoo.com.
authors.forename: Anca Maria
authors.initials: AM
authors.lastname: Cimpean
authors.affiliation: Department of Pathology, "Nicolae Testemiţanu" University of Medicine and Pharmacy, Chisinau, Moldova.
authors.forename: Eugen
authors.initials: E
authors.lastname: Melnic
authors.affiliation: Department of Endocrinology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Mihail
authors.initials: M
authors.lastname: Coculescu
authors.affiliation: Department of Microscopic Morphology/Histology, Angiogenesis Research Center "Victor Babes", University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Raluca Amalia
authors.initials: RA
authors.lastname: Ceauşu
authors.affiliation: Department of Microscopic Morphology/Histology, Angiogenesis Research Center "Victor Babes", University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Marius
authors.initials: M
authors.lastname: Raica
mesh_terms: D000236:Adenoma / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism
chemical_list: D006728:Hormones; D011388:Prolactin
keywords: Pituitary adenomas; angiogenesis; prolactinomas; tumor blood vessels