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

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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.

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Abbreviations

MEG3 :

Maternally expressed gene 3

GADD45γ :

Growth arrest and DNA damage-inducible gamma

qRT-PCR:

Quantitative reverse transcriptase

GH:

Growth hormone

PRL:

Prolactin

ACTH:

Adrenocorticotropic hormone

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Acknowledgments

We wish to thank Neuroendocrinology Center of Hospital São José, Irmandade Santa Casa de Misericórdia de Porto Alegre, Brazil, for providing the human pituitary tissues. This work was supported by CAPES (Coordenação de aperfeiçoamento de pessoal de nível superior), Ministry of Education, Brazil and UFCSPA (Universidade Federal de Ciências da Saúde de Porto Alegre), Porto Alegre, Brazil.

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Authors and Affiliations

  1. Post Graduation Program of Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, CEP 90050-170, Brazil

    Lisiane Cervieri Mezzomo, Paulo Henrique Gonzales, Miriam Costa Oliveira & Maria Beatriz Fonte Kohek

  2. Laboratory of Molecular Biology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil

    Lisiane Cervieri Mezzomo, Paulo Henrique Gonzales, Frederico Giacomoni Pesce, Nélson Kretzmann Filho & Maria Beatriz Fonte Kohek

  3. Neuroendocrinology Center of Santa Casa de Misericórdia, Porto Alegre, RS, Brazil

    Nelson Pires Ferreira & Miriam Costa Oliveira

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  1. Lisiane Cervieri Mezzomo
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Correspondence to Maria Beatriz Fonte Kohek.

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Mezzomo, L.C., Gonzales, P.H., Pesce, F.G. et al. Expression of cell growth negative regulators MEG3 and GADD45γ is lost in most sporadic human pituitary adenomas. Pituitary 15, 420–427 (2012). https://doi.org/10.1007/s11102-011-0340-1

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