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Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence

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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.

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Acknowledgments

This work was supported by a Pfizer grant and by Fundación Comunidad Valenciana Investigación HGUA.

Conflict of interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. Endocrinology Department, Hospital General Universitario Alicante, c/Pintor Baeza 12, 03010, Alicante, Spain

    Ruth Sánchez-Ortiga, Oscar Moreno-Perez & Antonio M. Picó Alfonso

  2. Research Unit, Hospital General Universitario Alicante, Alicante, Spain

    Laura Sánchez-Tejada

  3. Neurosurgery Department, Hospital Ribera, Valencia, Spain

    Pedro Riesgo

  4. Pathology Department, Hospital General Universitario Alicante, Alicante, Spain

    Maria Niveiro

Authors
  1. Ruth Sánchez-Ortiga
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  2. Laura Sánchez-Tejada
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  3. Oscar Moreno-Perez
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  4. Pedro Riesgo
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  5. Maria Niveiro
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  6. Antonio M. Picó Alfonso
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Corresponding author

Correspondence to Antonio M. Picó Alfonso.

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Ruth Sánchez-Ortiga and Laura Sánchez-Tejada contributed equally to this work.

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Sánchez-Ortiga, R., Sánchez-Tejada, L., Moreno-Perez, O. et al. Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence. Pituitary 16, 370–377 (2013). https://doi.org/10.1007/s11102-012-0434-4

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  • DOI: https://doi.org/10.1007/s11102-012-0434-4

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