Endocrine Abstracts

Thyroid cancer accounts for ca. 90% of all endocrine tumours and ca. 60% of endocrine cancer deaths, with an increasing incidence of the disease worldwide. Disease recurrence and metastasis occur in up to 20% of patients. Many of the tumour-initiating events of thyroid cancer have already been identified. Overexpression of Galectin-3 and telomerase, point mutations in RAS and BRAF, rearrangements of the PAX8-PPAR gamma and RET genes have all been implicated in thyroid tumour initiation and progression. Of the genetic alterations prevalent in thyroid tumours, several oncogenic changes are also specific to either papillary (e.g. BRAF) or follicular (e.g. Ras) thyroid tumours. Molecular markers offer the potential of increased sensitivity and discrimination over existing histological and cytological evaluations, specifically in the ability to discern the benign from the malignant, and the recurrent from the non-recurrent. In spite of the large number of biological markers proposed to improve the differential diagnosis between benign and malignant nodules, however, a real diagnostic and prognostic marker is still required.

Originally isolated from pituitary cells, PTTG is a novel marker showing enormous potential in the understanding of thyroid and other tumours. PTTG is a multifunctional gene with dual roles in tumourigenesis: first, through its action as a key regulator of mitosis, overexpression of PTTG initiates genetic instability; second, as a transactivator of growth factors, high PTTG expression induces FGF-2, VEGF and other pro-angiogenic genes. Thus, PTTG appears to be both an initiator and promoter of tumourigenesis, whose expression has been correlated with metastatic potential across a plethora of tumour types. Recently, a specific PTTG Binding Factor (PBF) has been identified, which is overexpressed in thyroid tumours, especially those which demonstrate recurrence. In common with PTTG, overexpression of PBF transforms murine NIH3T3 cells and induces tumours in nude mice. Together, PTTG and PBF represent novel molecular markers of thyroid cancer, with the exciting potential to predict future recurrence and metastasis.