Expression of angiogenic and proliferative factors in human pituitary adenomas

CAROLINA CRISTINA; M INÉS PÉREZ MILLÁN; RAUL DULCE; SILVIA BERNER; DAMASIA BECU VILLALOBOS

Washington DC

Congreso; The Endocrine Society´s annual meeting; 2009

Despite their benign nature, pituitary adenomas are frequently invasive and aggressive, causing neurological and endocrinological morbidity. Although there is controversy about the degree of vascularization that these adenomas possess, it is known that angiogenesis is a fundamental process for the tumor growth. In this study the relationship between proliferation and angiogenic factors was investigated in 45 human pituitaries adenomas. We evaluated the expression of VEGF and CD31 by Western Blot in adenoma samples (resistant macroprolactinomas, somatotropinomas, corticotropinomas and non functional adenomas (Table 1). All the adenomas expressed VEGF regardless of the type of tumor and there was no correlation between the expression pattern and age of patients (r2= 0.058, NS). We found a positive lineal correlation between VEGF and CD31 (N= 45, R2= 0.41; P=0.010). Another angiogenic and mitogenic factor, FGF-2, was evaluated by immunohistochemistry, and cytoplasmatic positivity was identified in 56% of the adenomas, and in some cases immunoreactivity was observed in the extracellular matrix. Proliferation markers were studied: PCNA by Western Blot and Ki-67 by immunohistochemistry. We did not observe differences between expression pattern of these markers and the hormonal immunotype of adenomas. Furthermore, there was no correlation between PCNA and CD31 (R2=0.0002; N=42), or PCNA and VEGF (R2= 0.0019; N=44), or between Ki67 and VEGF (R2=0.006; N=26), so in these benign adenomas the angiogenic process is not associated with the proliferation index. In conclusion, VEGF, present in all the samples studied, correlated with CD31 probably indicating that the generation of new vessels is required for the tumor growth. So VEGF could be an alternative therapeutic target, especially in highly vascularized adenomas. On the other hand, FGF-2 was present in only 56% of the adenomas. Lack of correlation of proliferation and angiogenic markers indicate that proliferation is not limited to the degree of vascularization, but it also depends on the genetic defect which gave origin to the adenoma. Understanding the mechanisms of angiogenic control of pituitary tumors could be useful for the prediction of tumor progression and treatment.