Abstract
Purpose
Gallbladder carcinoma (GC) is generally considered as a relatively rare malignancy with poor prognosis. In order to guide clinicians in selecting suitable treatment for GC patients, reliable markers predictive of poor clinical outcome are desirable. This study analyzed the expression of Polo-like kinase 1 (Plk1), Nima related kinases 7 (Nek7) and Forkhead box M1 (FoxM1) in GC tissues and their relationship to clinicopathologic features and survival.
Methods
We immunohistochemically investigated the 76 specimens of gallbladder carcinoma, pericarcinoma and normal tissues using Nek7, FoxM1 and Plk1 antibodies and analyzed the overall survival time of these 76 patients.
Results
There were significant correlations between the high level expression of Nek7, FoxM1 and Plk1 and the tumor differentiation, Nevin staging and metastasis. The high level expression of Nek7, FoxM1 and Plk1 was significantly associated with shorter overall survival time in univariate analysis (log-rank test), also identified as an independent prognostic factor in multivariate analysis.
Conclusion
Nek7, FoxM1 and Plk1 were significantly associated with certain clinicopathologic indices in GC. Evaluation of Nek7, FoxM1 and Plk1 expression may be an important factor in identifying a group of poor GC prognosis.
Similar content being viewed by others
References
Randi G, Malvezzi M, Levi F et al (2009) Epidemiology of biliary tract cancers: an update. Ann Oncol 20(1):146–159
Dixon E, Vollmer CM Jr, Sahajpal A et al (2005) An aggressive surgical approach leads to improved survival in patients with gallbladder cancer: a 12-year study at a North American Center. Ann Surg 241(3):385–394
Goldin RD, Roa JC (2009) Gallbladder cancer: a morphological and molecular update. Histopathology 55(2):218–229
Mikami T, Yanagisawa N, Baba H et al (1999) Association of Bcl-2 protein expression with gallbladder carcinoma differentiation and progression and its relation to apoptosis. Cancer 85(2):318–325
Pandey M, Sood BP, Shukla RC et al (2000) Carcinoma of the gallbladder: role of sonography in diagnosis and staging. J Clin Ultrasound 28(5):227–232
Janssen A, Medema RH (2011) Mitosis as an anti-cancer target. Oncogene 30(25):2799–2809
Nakagawa Y, Numoto K, Yoshida A et al (2006) Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization. J Cancer Res Clin Oncol 132(7):444–450
Song B, Liu XS, Liu X (2012) Polo-like kinase 1 (Plk1): an unexpected player in DNA replication. Cell Div 7:3
Degenhardt Y, Lampkin T (2010) Targeting Polo-like kinase in cancer therapy. Clin Cancer Res 16(2):384–389
O’Regan L, Fry AM (2009) The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis. Mol Cell Biol 29(14):3975–3990
Quarmby LM, Mahjoub MR (2005) Caught Nek-ing: cilia and centrioles. J Cell Sci 118(22):5161–5169
Ramakrishna S, Kim IM, Petrovic V et al (2007) Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor. Dev Dynam 236(4):1000–1013
Nevin JE, Moran TJ, Kay S et al (1976) Carcinoma of the gallbladder: staging, treatment, and prognosis. Cancer 37(1):141
Zhu AX, Hong TS, Hezel AF et al (2010) Current management of gallbladder carcinoma. Oncologist 15(2):168–181
Wang C, Zhao H, Lu J et al (2012) Clinicopathological significance of SOX4 expression in primary gallbladder carcinoma. Diagn Pathol 7:41
Wu LC, Chen LT, Tsai YJ et al (2012) Alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confers an independent prognostic indicator. J Clin Pathol 65(4):309–314
Zeng X, Shaikh FY, Harrison MK et al (2010) The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2. Oncogenec 29(36):5103–5112
Harrison MK, Adon AM, Saavedra HI (2011) The G1 phase Cdks regulate the centrosome cycle and mediate oncogene-dependent centrosome amplification. Cell Div 6:2
de Cárcer G, Manning G, Malumbres M (2011) From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle 10(14):2255–2262
Laoukili J, Stahl M, Medema RH (2007) FoxM1: at the crossroads of ageing and cancer. Biochim Biophys Acta 1775(1):92–102
Conflict of interest
There is no conflict of interest in this paper.
Author information
Authors and Affiliations
Corresponding author
Additional information
R. Wang and Y. Song contributed equally to this study and share first authorship.
Rights and permissions
About this article
Cite this article
Wang, R., Song, Y., Xu, X. et al. The expression of Nek7, FoxM1, and Plk1 in gallbladder cancer and their relationships to clinicopathologic features and survival. Clin Transl Oncol 15, 626–632 (2013). https://doi.org/10.1007/s12094-012-0978-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-012-0978-9