title: Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence.
abstract: Some pituitary adenomas (PA) demonstrate aggressive behavior with local invasion and recurrences. Angiogenesis is regarded as an essential step in the formation of solid tumors. The aim of this study is to find out whether angiogenic factors may have information about the aggressiveness of PA that could be useful in determining the frequency of follow-up and whether adjuvant therapy is necessary. In this retrospective descriptive study, we evaluated vascular endothelial growth factors (VEGF) and VEGF receptor (KDR) mRNA expression by RT-PCR analysis on 46 human PA samples. Clinical data, histological subtype and radiologic characteristics were studied to determine the associations between the variables and the pre-operative behavior of the tumor. In addition, we monitored 12 patients without adjuvant post-operative therapies over 46 months after surgery, determining progression of tumor remnants and its association with these markers. VEGF expression correlates with KDR expression (r = 0.40, p = 0.006). VEGF demonstrates different expression between histological subtypes (p = 0.036). The extension at magnetic resonance imaging showed that VEGF expression was related to suprasellar extension (p = 0.007), being expressed more on tumors with extrasellar growth than intrasellar ones (p = 0.008). Our results demonstrate a 27.5 times increased risk of extrasellar growth when VEGF expression exceeds 0.222 normalized copy number (NCN) (p = 0.002). Likewise, tumors with KDR greater than 0.750 NCN had less recurrence-free survival time (p = 0.032). Our results suggest that the expression of VEGF and its receptor could be a marker for poor outcome after partial tumor resection. These data should be considered in future studies evaluating angiogenic factors as therapeutic targets in patients with PA.
authors.affiliation: Endocrinology Department, Hospital General Universitario Alicante, c/Pintor Baeza 12, 03010, Alicante, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Sánchez-Ortiga
authors.forename: Laura
authors.initials: L
authors.lastname: Sánchez-Tejada
authors.forename: Oscar
authors.initials: O
authors.lastname: Moreno-Perez
authors.forename: Pedro
authors.initials: P
authors.lastname: Riesgo
authors.forename: Maria
authors.initials: M
authors.lastname: Niveiro
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Picó Alfonso
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor