title: Prognostic significance of Tiam1 expression in papillary thyroid carcinoma.
abstract: T lymphoma and metastasis gene 1 (Tiam1) is a guanine nucleotide exchange factor (GNEF) that regulates the guanosine triphosphatase to facilitate the exchange of guanosine diphosphate for guanosine triphosphate. It specifically activates Rac1, a member of the Rho family of GTPases. Tiam1 is involved in cell proliferation, cytoskeletal organization, cellular adhesion, and transcriptional activation. It has been suggested that alterations in Tiam1 expression might contribute to the progression of various human cancers. The usefulness of Tiam1 expression as a prognostic marker in papillary thyroid carcinoma (PTC) has not been investigated yet. The aim of this study was to analyze the expression of Tiam1 in PTC as well as its association with the clinicopathologic features and prognostic significance. Surgical tissue samples were taken from 106 PTC patients who had been followed up for at least 9.3 years. Strong expression of Tiam1 was detected in 54% of the cases. Tiam1 expression was associated significantly with various clinicopathologic parameters, such as gender (P=0.039), tumor multicentricity (P=0.0124), histologic subtype (P=0.0427), TNM stage (P=0.0151), and distant metastases at diagnosis (P=0.0001). Survival analysis showed that the Tiam1 low-expression group had a significantly shorter overall survival time than Tiam1 high-expression group (P=0.0007). Multivariate analysis showed that Tiam1 expression was a significant and independent prognostic indicator (P=0.0090) for PTC patients. Tiam1 expression may be a novel and independent prognostic marker of PTC patients.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, Kwei-Shan, Taoyuan, Taiwan. ch9211@adm.cgmh.org.tw
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Jen-Der
authors.initials: JD
authors.lastname: Lin
authors.forename: Chia-Fen
authors.initials: CF
authors.lastname: Yang
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Chao
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Sun
authors.forename: I-Chin
authors.initials: IC
authors.lastname: Wu
authors.forename: Ngan-Ming
authors.initials: NM
authors.lastname: Tseng
authors.forename: Shir-Hwa
authors.initials: SH
authors.lastname: Ueng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D018450:Disease Progression; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D020662:Guanine Nucleotide Exchange Factors; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human
references.citation: Oncogene. 1995 Apr 6;10(7):1371-6
references.pmid: 7731688
references.citation: Oncol Rep. 2011 Mar;25(3):841-8
references.pmid: 21186404
references.citation: Surgery. 1993 Dec;114(6):1050-7; discussion 1057-8
references.pmid: 8256208
references.citation: Int J Cancer. 2000 Nov 1;88(3):369-76
references.pmid: 11054665
references.citation: Science. 1997 Nov 21;278(5342):1464-6
references.pmid: 9367959
references.citation: World J Gastroenterol. 2005 Feb 7;11(5):705-7
references.pmid: 15655826
references.citation: Oncogene. 1995 Dec 7;11(11):2215-21
references.pmid: 8570171
references.citation: Ann Surg Oncol. 1996 Nov;3(6):534-8
references.pmid: 8915484
references.citation: J Cell Biol. 1999 Nov 29;147(5):1009-22
references.pmid: 10579721
references.citation: Br J Cancer. 2006 Oct 23;95(8):1081-6
references.pmid: 17003780
references.citation: J Biol Chem. 2004 Jul 16;279(29):30092-8
references.pmid: 15138270
references.citation: World J Surg. 2002 Aug;26(8):879-85
references.pmid: 12016468
references.citation: Breast Cancer Res Treat. 2004 Mar;84(1):21-32
references.pmid: 14999151
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):784-91
references.pmid: 19240234
references.citation: JAMA. 2006 May 10;295(18):2164-7
references.pmid: 16684987
references.citation: J Clin Endocrinol Metab. 1990 Aug;71(2):414-24
references.pmid: 2380337
references.citation: ORL J Otorhinolaryngol Relat Spec. 2009;71(3):163-71
references.pmid: 19506399
references.citation: Mod Pathol. 2008 May;21(5):544-52
references.pmid: 18246045
references.citation: Histopathology. 2006 Jun;48(7):787-94
references.pmid: 16722926
references.citation: J Biol Chem. 2001 Jul 27;276(30):28443-50
references.pmid: 11328805
references.citation: Nature. 1995 May 25;375(6529):338-40
references.pmid: 7753201
references.citation: Cell. 1994 May 20;77(4):537-49
references.pmid: 7999144
references.citation: Int J Cancer. 2009 Feb 1;124(3):653-8
references.pmid: 18972435
references.citation: Nature. 2002 Jun 20;417(6891):867-71
references.pmid: 12075356
references.citation: J Biol Chem. 2001 Nov 9;276(45):41889-97
references.pmid: 11551917