Endocrine Abstracts

Pituitary neuroendocrine tumors (PitNETs) are typically benign tumors presenting with symptoms related to hormone hypersecretion and/or intracranial mass. Current classification of PitNETs is based on the immunohistochemical expression of adenohypophysial hormones and three main pituitary-specific transcriptions factors PIT1, TPIT and SF1. PitNETs usually remain intrasellar, however, 20-40% of tumors show invasiveness into cavernous sinus and 6–8% infiltrate into the bones, affecting the prognosis. There is an unmet need to detect reliable biomarkers that can predict the parasellar and bone invasiveness of PitNETs as well as the factors related to tumor vascularization. We validated the current PitNETs classification by exploring gene expression patterns in a well-characterized cohort of 51 PitNETs of different histological and clinical types. The gene expression signatures were compared with clinical and immunohistochemically based classification. Next, we extended the cohort to acquire a higher fraction of invasive tumors. Applying the same transcriptomics analysis in this expanded cohort of 77 patients we studied the gene expression differences between invasive and non-invasive tumors regarding parasellar and bone-invasiveness. Moreover, we explored the genes that correlated to the contrast enhancement quotient, a radiological proxy of tumor vascularization. Our results revealed three main transcriptomics clusters of PitNETs, supporting the current immunohistochemical PitNETs classification. A few “null cell adenomas” clustered as either gonadotroph or corticotroph tumors, further questioning this controversial entity. Our results did not demonstrate clear clustering regarding the invasiveness. However, differentially expressed genes related to parasellar growth were genes with previously established role in tumor invasiveness, and the differentially expressed genes regarding bone invasiveness were those involved in anti-tumoral immune response and NF-κB pathway. Several genes involved in tumor biology and vascularization correlated significantly with the contrast enhancement quotient. In conclusion, we demonstrated that the current WHO classification of PitNETs based on the immunohistochemical expression of PIT1, TPIT and SF1 is in concordance with the three PitNETs subtypes with distinct gene expression patterns. The transcriptomic analysis also revealed differences in the molecular landscape between invasive and non-invasive PitNETs. However, a clear clustering was not demonstrated, which may, at least partly, be explained by the strong influence of the genes that drive the cell lineage differentiation in our diverse cohort of PitNETs. The contrast enhancement quotient appears as a novel potential radiological parameter of tumor vascularization. Several detected tumor-driving genes and genes related to the invasiveness and vascularization of PitNETs are potential therapeutic targets and prognostic biomarkers, thus warranting further research.