Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors

Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas. We aimed to evaluate the expression of EMT-related markers in 72 NF-PitNET and 16 non-tumoral pituitaries. To further explore the potential usefulness of medical treatment for NF-PitNET we assessed the expression of somatostatin receptors and dopamine-associated genes. We found that SNAI1, SNAI2, Vimentin, KLK10, PEBP1, Ki-67 and SSTR2 were associated with invasive NF-PitNET. Furthermore, we found that the EMT phenomenon was more common in NF-PitNET than in GH-secreting pituitary tumors. Interestingly, PEBP1 was overexpressed in recurrent NF-PitNET, and could predict growth recurrence with 100% sensitivity but only 43% specificity. In parallel with previously reported studies, SSTR3 is highly expressed in our NF-PitNET cohort. However, SSTR3 expression is highly heterogeneous among the different histological variants of NF-PitNET with very low levels in silent corticotroph adenomas. NF-PitNET showed an enhanced EMT phenomenon. SSTR3 targeting could be a good therapeutic candidate in NF-PitNET except for silent corticotroph adenomas, which express very low levels of this receptor. In addition, PEBP1 could be an informative biomarker of tumor regrowth, useful for predictive medicine in NF-PitNET

Endocrine Late Effects in Childhood Cancer Survivors

Childhood cancer management has improved considerably over the years, leading to a significant improvement in survival of up to 80%. However, childhood cancer survivors are at the highest risk of developing sequelae resulting from treatment, with endocrine complications being frequently observed among survivors. Multiple predisposing factors for endocrine sequelae have been identified, including age at diagnosis, treatment received, radiation, tumor type, and genetic polymorphisms, which could explain the individual predisposition to develop drug toxicity. Novel agents targeting tumor growth and immune checkpoint inhibitors have recently become the cornerstone for the treatment of different cancers, triggering a myriad of immune-related endocrinopathies. Endocrine sequelae of cancer therapy will have an impact on not only childhood but also on the survival and quality of life of these highly complex patients. Therefore, lifelong monitoring of childhood cancer survivors at risk of endocrine diseases is paramount. Encouraging oncologists and endocrinologists to develop new follow-up and early detection guidelines that minimize sequelae among these patients has become a priority, promoting integration between pediatric and adult units since many sequelae may manifest only after years to decades of follow-up