This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boelaert, K. Articles by Franklyn, J. A. Search for Related Content PubMed PubMed Citation Articles by Boelaert, K. Articles by Franklyn, J. A.

Pituitary Tumor Transforming Gene and Fibroblast Growth Factor-2 Expression: Potential Prognostic Indicators in Differentiated Thyroid Cancer

Divisions of Medical Sciences (K.B., C.J.M., L.A.T., N.J.L.G., J.C.W., M.C.S., J.A.F.) and Immunity and Infection (A.R.B.), University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom; and Department of Statistics (R.L.H.), University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

Address all correspondence and requests for reprints to: Dr. K. Boelaert, Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom. E-mail: k.boelaert{at}bham.ac.uk.

Abstract

Differentiated thyroid cancers are the most common endocrine cancers, but there are no reliable molecular markers of prognosis. Pituitary tumor transforming gene (PTTG) plays several potential roles in tumor initiation and progression, including regulating mitosis and stimulating expression of fibroblast growth factor (FGF)-2. Increased expression of PTTG has been demonstrated in follicular thyroid lesions, and expression of this oncogene has been identified as a potential prognostic marker in pituitary adenomas and colon carcinomas. We assessed the expression of PTTG and FGF-2 and its receptor FGF-R-1 in 27 differentiated thyroid cancers, and we compared this with expression in 11 normal thyroids, 25 multinodular goiters, and 13 Graves’ disease specimens. We also examined the relationship between gene expression and clinical markers of tumor behavior. PTTG and FGF-2 were overexpressed in thyroid carcinomas (9.5-fold increase, P = 0.003, and 5.0-fold increase, P < 0.001, respectively) compared with normal thyroid. Increased FGF-2 mRNA expression was independently associated with the findings of lymph node invasion (R² = 0.71; P < 0.001) and distant metastasis (R² = 0.55; P = 0.009) at tumor presentation, after taking into account known prognostic factors such as age and gender of the patient and size and type of the tumor. High PTTG expression was independently associated with tumor recurrence (R² = 0.64; P = 0.003). We conclude that PTTG and FGF-2 expression are potential prognostic markers (and perhaps therapeutic targets) for differentiated thyroid cancer.

Footnotes

Abbreviations: FGF, Fibroblast growth factor; PCNA, proliferating cell nuclear antigen; PTTG, Pituitary tumor transforming gene; TNM, tumor node metastasis.

This article has been cited by other articles:

				F. Salehi, K. Kovacs, B. W Scheithauer, R. V Lloyd, and M. Cusimano Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update Endocr. Relat. Cancer, September 1, 2008; 15(3): 721 - 743. [Abstract] [Full Text] [PDF]

				T. Ito, Y. Shimada, T. Kan, S. David, Y. Cheng, Y. Mori, R. Agarwal, B. Paun, Z. Jin, A. Olaru, et al. Pituitary Tumor-Transforming 1 Increases Cell Motility and Promotes Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma Cancer Res., May 1, 2008; 68(9): 3214 - 3224. [Abstract] [Full Text] [PDF]

				G. Vlotides, T. Eigler, and S. Melmed Pituitary Tumor-Transforming Gene: Physiology and Implications for Tumorigenesis Endocr. Rev., April 1, 2007; 28(2): 165 - 186. [Abstract] [Full Text] [PDF]

				D.S. Kim, J.A. Franklyn, V.E. Smith, A.L. Stratford, H.N. Pemberton, A. Warfield, J.C. Watkinson, T. Ishmail, M.J.O. Wakelam, and C.J. McCabe Securin induces genetic instability in colorectal cancer by inhibiting double-stranded DNA repair activity Carcinogenesis, March 1, 2007; 28(3): 749 - 759. [Abstract] [Full Text] [PDF]

				G. Vlotides, M. Cruz-Soto, T. Rubinek, T. Eigler, C. J. Auernhammer, and S. Melmed Mechanisms for Growth Factor-Induced Pituitary Tumor Transforming Gene-1 Expression in Pituitary Folliculostellate TtT/GF Cells Mol. Endocrinol., December 1, 2006; 20(12): 3321 - 3335. [Abstract] [Full Text] [PDF]

				D. S. Kim, J. A. Franklyn, K. Boelaert, M. C. Eggo, J. C. Watkinson, and C. J. McCabe Pituitary Tumor Transforming Gene (PTTG) Stimulates Thyroid Cell Proliferation via a Vascular Endothelial Growth Factor/Kinase Insert Domain Receptor/Inhibitor of DNA Binding-3 Autocrine Pathway J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4603 - 4611. [Abstract] [Full Text] [PDF]

				N G. de la Torre, I Buley, J A H Wass, and H E Turner Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour. Endocr. Relat. Cancer, September 1, 2006; 13(3): 931 - 944. [Abstract] [Full Text] [PDF]

				J. Tfelt-Hansen, D. Kanuparthi, and N. Chattopadhyay The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin. Med. Res., June 1, 2006; 4(2): 130 - 137. [Abstract] [Full Text] [PDF]

				C. Saez, M. A. Martinez-Brocca, C. Castilla, A. Soto, E. Navarro, M. Tortolero, J. A. Pintor-Toro, and M. A. Japon Prognostic Significance of Human Pituitary Tumor-Transforming Gene Immunohistochemical Expression in Differentiated Thyroid Cancer J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1404 - 1409. [Abstract] [Full Text] [PDF]

				D. S. Kim, J. A. Franklyn, A. L. Stratford, K. Boelaert, J. C. Watkinson, M. C. Eggo, and C. J. McCabe Pituitary Tumor-Transforming Gene Regulates Multiple Downstream Angiogenic Genes in Thyroid Cancer J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1119 - 1128. [Abstract] [Full Text] [PDF]

				X. Huang, R. Hatcher, J. P. York, and P. Zhang Securin and Separase Phosphorylation Act Redundantly to Maintain Sister Chromatid Cohesion in Mammalian Cells Mol. Biol. Cell, October 1, 2005; 16(10): 4725 - 4732. [Abstract] [Full Text] [PDF]

				A. L. Stratford, K. Boelaert, L. A. Tannahill, D. S. Kim, A. Warfield, M. C. Eggo, N. J. L. Gittoes, L. S. Young, J. A. Franklyn, and C. J. McCabe Pituitary Tumor Transforming Gene Binding Factor: A Novel Transforming Gene in Thyroid Tumorigenesis J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4341 - 4349. [Abstract] [Full Text] [PDF]

				S.-J. Tsai, S.-J. Lin, Y.-M. Cheng, H.-M. Chen, and L.-Y. C. Wing Expression and Functional Analysis of Pituitary Tumor Transforming Growth Factor-1 in Uterine Leiomyomas J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3715 - 3723. [Abstract] [Full Text] [PDF]

				R. St. Bernard, L. Zheng, W. Liu, D. Winer, S. L. Asa, and S. Ezzat Fibroblast Growth Factor Receptors as Molecular Targets in Thyroid Carcinoma Endocrinology, March 1, 2005; 146(3): 1145 - 1153. [Abstract] [Full Text] [PDF]

				S. Ezzat, P. Huang, A. Dackiw, and S. L. Asa Dual Inhibition of RET and FGFR4 Restrains Medullary Thyroid Cancer Cell Growth Clin. Cancer Res., February 1, 2005; 11(3): 1336 - 1341. [Abstract] [Full Text] [PDF]

				K Boelaert, R Yu, L A Tannahill, A L Stratford, F L Khanim, M C Eggo, J S Moore, L S Young, N J L Gittoes, J A Franklyn, et al. PTTG's C-terminal PXXP motifs modulate critical cellular processes in vitro J. Mol. Endocrinol., December 1, 2004; 33(3): 663 - 677. [Abstract] [Full Text] [PDF]

				J. Tfelt-Hansen, S. Yano, S. Bandyopadhyay, R. Carroll, E. M. Brown, and N. Chattopadhyay Expression of Pituitary Tumor Transforming Gene (PTTG) and Its Binding Protein in Human Astrocytes and Astrocytoma Cells: Function and Regulation of PTTG in U87 Astrocytoma Cells Endocrinology, September 1, 2004; 145(9): 4222 - 4231. [Abstract] [Full Text] [PDF]

				K. BOELAERT, L. A. TANNAHILL, J. N. BULMER, S. KACHILELE, S. Y. CHAN, D. KIM, N. J. L. GITTOES, J. A. FRANKLYN, M. D. KILBY, and C. J. MCCABE A potential role for PTTG/securin in the developing human fetal brain FASEB J, September 1, 2003; 17(12): 1631 - 1639. [Abstract] [Full Text] [PDF]