Contribution of the molecular biology to the study of the behaviour of pituitary adenomas
Laura Sánchez-Tejada1, Ruth Sánchez-Ortiga2, Maria Niveiro3, Gloria Peiro3, Oscar Moreno2, Ignacio Aranda3 & Antonio A Pico Alfonso3
Background: There is an increasing interest to find specific prognostic markers of the aggressive behaviour of some pituitary adenomas (PA). The most studied markers have been the immunohistochemical staining for Ki-67 and p53. The aim of this study was to evaluate the relevance as possible prognostic markers of growth factors (IGF1R), angiogenic factors (VEGF and his receptor) and new genes (PTTG) versus the immunohistochemical expression of Ki-67 and p53 in PA.
Design: In this retrospective descriptive study, we analyzed 56 human PA samples: 32 gonadotrophic (GT), 6 corticotrophic (CT), 6 somatotrophic (ST), 4 lactotrophic (LT), 1 thyrotrophic (TT), 1 null-cell and 6 GH-PRL-secreting adenomas (GLT), based on OMS 2004 classification. We evaluated the VEGF, VEGFR, PTTG and IGF1R mRNA expression by quantitative real-time PCR using Taqman technology and TaqMan Gene Expression Assays (Applied Biosystems). Immunohistochemical (IHC) staining was performed in whole sections for ER (cut-off 10%), Ki-67 and p53 (cut-off 20%). In addition we revised the extension in magnetic resonance imaging of 17 patients. The Student t-test was used for statistical analysis.
Results: We observed than the histology subtype GT had the highest expression of VEGF (P=0.007), VEGFR (P=0.011) and IGF1R (P=0.003) while CT had the lowest expression of these genes (P=0.021, P=0.004 and P=0.026 respectively). The expression of PTTG was decreased in the TT adenoma respect the above of the other subtypes (P=0.045). Overexpression of p53 was positively correlated with the level of VEGF and VEGFR expression (P=0.001 and P=0.02). The tumors with diffuse extension shown association with more IGF1R expression (P=0.003) but there was no correlation with Ki-67, p53 or ER status.
Conclusions: Our preliminary findings suggest that these genes behave differently depending on the histological subtype and that some of them could report more information about the behaviour of PA than the expression for Ki-67 or p53.