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Pituitary Tumor Transforming Gene Binding Factor: A Novel Transforming Gene in Thyroid Tumorigenesis

Division of Medical Sciences (A.L.S., K.B., L.A.T., D.S.K., M.C.E., N.J.L.G., J.A.F., C.J.M.), Department of Pathology (A.W.), and Institute for Cancer Studies (L.S.Y.), University of Birmingham, Birmingham, B15 2TH, United Kingdom

Address all correspondence and requests for reprints to: Dr. C. J. McCabe, Division of Medical Sciences, Institute for Biomedical Research, University of Birmingham, Birmingham, B15 2TH, United Kingdom. E-mail: mccabcjz{at}bham.ac.uk.

Context: There are currently no clear markers for the detection of differentiated thyroid cancer and its recurrence. Pituitary tumor transforming gene (PTTG) is a protooncogene implicated in the pathogenesis of multiple tumor types, which stimulates fibroblast growth factor-2 secretion via PTTG binding factor (PBF).

Objective: The aim of this study was to ascertain whether 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 the ability of PBF to transform cells and form tumors in nude mice and its subcellular localization.

Setting: The study was conducted at a 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: No intervention was conducted.

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

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 up-regulate 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 sc overexpression of PBF induced tumor formation in athymic nude mice.

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

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