Endocrine Abstracts

Introduction: Recently we have demonstrated the contribution of the quantification of expression of adenohypophyseal hormone genes in the identification of the different Pituitary Neuroendocrine Tumor (PitNET) subtypes according to the 2004 WHO criteria.

Aim: The aim of the present study was to evaluate the contribution of the quantification of expression of pituitary transcription factor genes to the identification of PitNETs according to 2017 WHO criteria.

Methods: From our collection of 300 PitNETs, we selected 93 tumors with complete clinical, immunohistochemical and molecular information with sufficient quality and quantity of remmanent biological material. In this study, we are reporting preliminary results of 41 tumors analyzed to date. The series analyzed include 6 corticotropinomas (CT), 7 somatotropinomas (3 mixed GH-PRL), 3 thyrotropinomas (TT), 14 gonadotropinomas (GT), 4 plurihormonal tumors (PH), 5 null cell tumors and 2 samples initially considered as normal pituitary gland. We quantified the gene expression of TBX19 (Tpit), POU1F1 (Pit1), SF1, GATA2 and ESR1 by quantitative real-time-PCR (qRT-PCR). The relative differences in gene expression were expressed as fold change and were obtained with the 2^-ΔΔCt method. We relied on the dominant gene expression in the qRT-PCR of the transcription factors to identify the different subtypes of PitNETs.

Results: All ST (pure and mixed) and TT PitNETs predominantly expressed POU1F1 (Pit1), confirming the previous molecular identification. Thirteen out of 14 GT expressed dominantly GATA2, confirming the GT lineage. The remaining tumour expressed NEUROD1 suggesting a CT cell origin. Five out of 6 CT expressed TBX19 (Tpit), verifying the CT origin. One CT expressed GATA2, suggesting a GT cell origin. t Two out of 5 null cell tumors, expressed SF1 and 1 expressed GATA2 suggesting a GT origin. The last two expressed both, NEUROD1 and GATA2, indicating a CT-GT lineage. Among the 4 PH tumors, 3 expressed POU1F1 (Pit1) and one expressed GATA2. Finally, one of the 2 samples initially considered as normal pituitary gland was identified as GT, since it predominantly expressed GATA2, while the other sample was confirmed as normal tissue.

Conclusion: In conclusion the molecular quantification of pituitary transcription factors validates the strength of our previous results of the contribution of the study of the expression of the adenohypophyseal hormone genes in the identification of PitNET subtypes. Moreover, allows us to reclassify the null cell and plurihormonal tumors and suggest the existence of a corticotroph-gonadotroph subtype. The complete series with molecular an immunohistochemical results will be presented in the congress.