Endocrine Abstracts

Introduction: Various tumours have a worse prognosis in male than in female. This is also true for lactotroph tumours. Indeed it is known that aggressive and malignant tumours, resistant to dopamine agonists, are more frequent in male than female and are associated to lower ESR1 expression.

Objectives: Our aims are to study the genes differentially expressed and the chromosomic alterations in lactotroph tumours between male and female and their relationships with estrogen pathway.

Material and methods: We compared 30 lactotroph tumours in male (n=20) and female (n=10). They were classified into 5 grades: benign (grades 1a-1b), invasive (grade 2a), suspected of malignancy (grade 2b) and malignant with metastasis (grade 3). The differential gene expression of all tumours were analyzed with CodeLink Uniset Human Whole Genome bioarrays. The chromosomic alterations using Affymetrix Genome-wide human SNP array 6.0 chip were compared in twelve of them (6 males and 6 females). The differences according to the sex, and the pathological classification was functionaly analysed with Ingenuity pathway analysis (Qiagen).

Results: In these lactotroph tumours, functional analysis of significantly deregulated genes (P value <0.05) showed that cell morphology, cell growth and proliferation, development and cell movement are significantly different between male and female. Among the genes significantly differentially expressed, 120 genes are increased and 20 genes are decreased (fold changes at least 2). Some genes as CTAG2, FGF13 and VEGF-D located on the X chromosome are particularly dysregulated in these tumours. Some of them are involved in the estrogen receptors pathway. CGH analysis highlighted the deletion of the 11 chromosome in 5/6 aggressive and malignant tumours in both sexes, and one chromosomic insertion into aggressive lactotroph tumours only in male. If we compare transcriptomic and CGH analysis, two genes are up regulated in man lactotroph tumours and located on inserted chromosomic region. Both genes are implicated in cell growth and proliferation and may be related to estrogen receptors pathway.

Conclusion: This integrative study demonstrates a sexually dimorphic gene expression and chromosomic alterations in lactotroph pituitary tumours. The differentially expressed genes are implicated in tumour growth, invasion and malignancy and some of them are in relation with the estrogen receptors pathway.