Expression of cell growth negative regulators MEG3 and GADD45γ is lost in most sporadic human pituitary adenomas

Abstract

We aimed at the evaluation of MEG3 and GADD45γ expression in sporadic functioning and clinically non-functioning human pituitary adenomas, morphologically characterized by immunohistochemistry analysis and their association with clinical features. Thirty eight patients who had undergone hypophysectomy at São José Hospital of Irmandade Santa Casa de Misericórdia in Porto Alegre, Brazil, were included in this study. We evaluated tumor-type specific MEG3 and GADD45γ expression by qRT-PCR in the pituitary adenomas, and its association with clinical features, as age, gender and tumor size, obtained from medical records. The patients consisted of 21 males and 17 females and the mean age was 47 ± 14 (mean ± SD), ranging from 18 to 73 years-old. Of these 14 were clinically non-functioning, 10 GH-secreting, 9 PRL-secreting, and 5 ACTH-secreting pituitary adenomas. All samples were macroadenomas, except four ACTH-secreting tumors, which were microadenomas. In summary, MEG3 and GADD45γ expression was significantly lost in most clinically non-functioning adenomas (78 and 92%, respectively). Other assessed pituitary tumor phenotypes expressed both genes at significantly different levels, and, in some cases, with overexpression. There was no significant association between gene expression and the analyzed clinical features. Our results confirm the previous report, which indicated that MEG3 and GADD45γ expression is lost in the majority of human pituitary tumors, mainly in clinically-nonfunctioning adenomas. Functioning tumors had differences of relative expression levels. The two groups of tumors are probably genetically different and may have a different natural history.