Context: There are currently no clear markers for the detection of differentiated thyroid cancer and its recurrence. PTTG is a proto-oncogene implicated in the pathogenesis of multiple tumor types, which stimulates FGF-2 secretion via its binding factor PBF.

Objective: To ascertain if PBF expression is associated with thyroid cancer outcome.

Design: PBF expression was measured at the mRNA and protein level. Tissue was collected during surgery with normal samples being taken from the contralateral lobe. In vitro studies ascertained PBF's ability to transform cells, form tumors in nude mice and its subcellular localization.

Setting: Primary care/ referral center.

Patients: Thyroid tumors were collected from a series of 27 patients undergoing surgical excision of papillary and follicular thyroid tumors.

Intervention: None.

Main Outcome Measure: The expression of PBF in thyroid cancers compared to normal thyroid, hypothesized before the investigation to be raised in tumors.

Results: PBF mRNA expression was higher in differentiated thyroid carcinomas than in normal thyroid (P < 0.001, N = 27), and was independently associated with tumor recurrence (P = 0.002, R² = 0.49). PTTG was able to upregulate PBF mRNA expression in vitro (P < 0.001, N = 12), and stable overexpression of PBF in NIH3T3 cells resulted in significant colony formation (P < 0.001, N = 12). In vivo, stable subcutaneous overexpression of PBF induced tumor formation in athymic nude mice.

Conclusions: PBF is an additional prognostic indicator in differentiated thyroid cancer which is transforming in vitro and tumorigenic in vivo.