Log in |
Jen-Wei Tsai MD, Chien-Feng Li MD, Yu-Chien Kao MD, Jun-Wen Wang MD, Fu-Min Fang MD, PhD, Yu-Hui Wang MS, Wen-Ren Wu, Li-Ching Wu, Chung-Hsi Hsing MD, Shau-Hsuan Li MD, Shih-Chen Yu BS, Jui Lan MD, Hsuan-Ying Huang MD
Bone and Soft Tissue Sarcomas
View full article HTML | View full article PDF | Download Citation
Myxofibrosarcoma is genetically complex and remains obscure in molecular determinants of clinical aggressiveness. Our prior study revealed recurrent gains of 7q in myxofibrosarcomas where MET and CDK6 genes displayed increased DNA copies. Previously, we demonstrated the implication of MET overexpression, prompting us to further elucidate the roles of CDK6 in myxofibrosarcomas.
On tissue microarrays, CDK6 immunoexpression was assessable in 77 primary tumors, 55 of which were successfully quantified for CDK6 and MET genes by real-time PCR using genomic DNA extracted from laser-microdissected tumor cells. Gene status and protein expression of CDK6 were correlated with each other, clinicopathological variables, metastasis-free survival (MFS), and disease-specific survival (DSS).
Protein overexpression and gene amplification of CDK6, which were detected in 21 of 77 (27.2 %) and 13 of 55 cases (23.6 %), respectively, were highly related to each other (p < .001) and associated with higher grades (overexpression, p = .004; amplification, p = .014). There was a strong correlation between CDK6 and MET gene copies (p < .001, r = 0.0714). Importantly, CDK6 protein overexpression (MFS, p = .0002; DSS, p = .0015) and gene amplification (MFS, p = .0001; DSS, p = .0083) were both univariately associated with worse outcomes. Together with nonextremity location and AJCC stage III disease, CDK6 overexpression independently portended inferior MFS (p = .0015, risk ratio [RR] = 7.411). This aberration, along with nonextremity location, was also an independent adverse prognosticator of DSS (p = .0069, RR = 6.006).
In approximately a quarter of primary myxofibrosarcomas, CDK6 overexpression is mostly driven by gene amplification on 7q, associated with adverse prognosticators, and independently predictive of worse outcomes, highlighting its possible causative role in tumor aggressiveness.
Go to Issue Contents
Add this article to your Personal Archive
Effective January 2013, there will be a processing fee of $50 USD for each initial new submission of an Annals article, excluding editorials. Submitted new manuscripts will not enter the review process until the submission fee has been paid. . There will be no processing fee associated with resubmitted manuscripts.
HIGHLIGHTED VIDEO OF THE MONTH
Lymphatic Mapping and Sentinel Node Biopsy in the Colonic Mesentery by Natural Orifice Transluminal Endoscopic Surgery (NOTES) by R. A. Cahill MD, FRCS, S. Perretta MD, J. Leroy MD, B. Dallemagne MD, and J. Marescaux MD, FRCS, FACS. Annals of Surgical Oncology. Volume 15, Number 10, DOI: 10.1245/s10434-008-9952-8
Annals of Surgical Oncology is copyrighted by the Society of Surgical Oncology
© Springer Healthcare Ltd. A part of Springer Science+Business Media